HLA class-I and HLA class-II phenotypic, gene and haplotypic frequencies in Tunisians by using molecular typing data

The aim of this study is to define a reliable reckoning of gene frequencies and six-locus haplotypic frequencies of HLA-A, HLA-B, HLA-C, HLA-DRB1, HLA-DQA1, HLA-DQB1 and HLA-DPB1 in the Tunisian population. One hundred unrelated random, healthy people originating from various parts of Tunisia were typed for the alleles of the loci mentioned above by using the molecular techniques polymerase chain reaction--hybridization with oligonucleotide probe (PCR-SSO) and sequence specific primers (SSP). The population studied appeared to be in Hardy-Weinberg equilibrium. Allelic frequency distributions were observed at each locus. The most frequent HLA-A alleles were HLA-A*02 (39%) HLA-A*0101 (25%), HLA-A*30 (21%) and HLA-A*2301 (18%). Moreover, HLA-3A*3601, HLA-1A*6601, HLA-1A*3402 and HLA-2A*8001 were found; however, no HLA-A*4301 was detected. For the HLA-B locus, the most common in descending order were HLA-B*44 (22%), HLA-B*5001 (19%), HLA-B*51 (16%) and HLA-B*18 (15%). Among the 28 alleles HLA-Cw detected, HLA-Cw*6 and HLA-Cw*7 were highly predominant with the frequencies of 33 and 30%, respectively. For the HLA class-II loci, HLA-DRB1*0701, HLA-DRB1*11, HLA-DRB1*13 and HLA-DRB1*03 were the most frequent DR alleles. For the HLA-DPB1, HLA-DPB1*0401, HLA-DPB1*0301 and HLA-DPB1*0201 were the most frequent DP alleles. Many haplotypes were in a strong positive-linkage disequilibrium. The most frequent haplotypes for HLA-A, HLA-B, HLA-C and HLA-DRDQ were HLA-A*3301, HLA-B*1402, HLA-Cw*0802, HLA-DRB1*0102, HLA-DQA1*0101 and HLA-DQB1*0501; HLA-A*2402, HLA-B*0801, HLA-Cw*0702, HLA-DRB1*0301, HLA-DQA1*0501 and HLA-DQB1*0201; HLA-A*2902, HLA-B*4403.1, HLA-Cw*1601, HLA-DRB1*0701, HLA-DQA1*0201 and HLA-DQB1*0202; HLA-A*3002, HLA-B*1801, HLA-Cw*0501, HLA-DRB1*0301, HLA-DQA1*0501 and HLA-DQB1*0201, with frequencies between 0.025 and 0.015. These data can be used as control data for HLA disease associations and paternity studies, but they are also important for the evaluation of the probability rate of success in determining the optimal matched donor in unrelated stem transplantation for Tunisian patients or patients of Tunisian origin.     

HLA-A, -B, -C and -DRB1 allele and haplotype frequencies in the Macedonian population based on a family study

Aim

The aim of this study was to determine HLA allele and 2-, 3- and 4-loci haplotype frequencies in a sample from Macedonian population with defined haplotypes based on family history.

Heterogeneity of rheumatoid arthritis: from phenotypes to genotypes

Rheumatoid arthritis (RA) is now recognized as a multigene disorder with a number of genetic polymorphisms contributing to disease pathogenesis. Here, we propose that the diagnostic category of RA includes multiple subtypes of disease and that the different phenotypes of RA correlate to different genotypes. Support for this concept has come from a reappraisal of the clinical heterogeneity of RA and the observation that HLA-DRB 1 polymorphisms are useful in describing genetic heterogeneity of RA phenotypes. A series of HLA-DRB 1 genes has been identified as RA associated, and in recent years emphasis has been put on the sequence similarities of these alleles. An alternative view focuses on the amino acid variations found in RA-associated HLA-DRB 1 alleles with different alleles being enriched in distinct subtypes of RA. Rheumatoid factor-positive destructive joint disease is predominantly associated with the HLA-DRB1*0401 allele, while HLA-DRB 1*0404 and B1*0101 predispose for milder and often seronegative disease. Expression of disease-associated alleles on both haplotypes carries a high risk for extra-articular manifestations. In particular, patients homozygous for HLA-DRB1*0401 frequently develop rheumatoid vasculitis on follow-up. Besides HLA gene polymorphisms, abnormalities in the generation and function of CD4 T cells and in inflammatory pathways established in synovial lesions can be used to dissect patient subsets with different variants of RA. Emergence of CD28-deficient CD4 T cells identifies RA patients with extra-articular manifestations. These cells undergo clonal expansion in vivo, produce high amounts of IFN-, and exhibit autoreactivity. Concordance of monozygotic twins for the expression of CD4⁺ CD28^– T cells suggests a role for genetic factors in the generation of these unusual T cells. Evidence for heterogeneity of the synovial component of RA comes from studies describing three distinct patterns of lymphoid organization in the synovium. Based upon the topography of tissue-infiltrating mononuclear cells, diffuse, follicular, and granulomatous variants of rheumatoid synovitis can be distinguished. Each pattern of lymphoid organization correlates with a unique profile of tissue cytokines, demonstrating that several pathways of immune deviation modulate disease expression in RA. A dissection of RA variants would have major implications on how the disease is studied, treated, and managed. Identifying combinations of RA risk genes that correlate with disease variants could, therefore, become an important diagnostic tool.     

Comparison of therapeutic effects between drainage blood reinfusion and temporary clamping drainage after total knee arthroplasty in patients with rheumatoid arthritis

OBJECTIVE:

To compare the therapeutic effects between drainage blood reinfusion and temporary clamping drainage after total knee arthroplasty in patients with rheumatoid arthritis to provide a basis for clinical practice.

METHODS:

Data from 83 patients with rheumatoid arthritis undergoing total knee arthroplasty were retrospectively analyzed. The 83 patients were divided into a drainage blood reinfusion group (DR group, n = 45) and a temporary clamping drainage group (CD group, n = 38). In the DR group, postoperative drainage blood was used for autotransfusion. In the CD group, closed drainage was adopted, and the drainage tube was clamped for 2 h postoperatively followed by patency. The postoperative drainage amount, hemoglobin level, rate and average volume of allogeneic blood transfusion, swelling and ecchymosis of the affected knee joint, time to straight-leg raising and range of active knee flexion were compared between the two groups.

RESULTS:

The total drainage volume was higher in the DR group than in the CD group (P = 0.000). The average volume of postoperative allogeneic blood transfusion (P = 0.000) and the decrease in the hemoglobin level 24 h after total knee arthroplasty (P = 0.012) were lower in the DR group than in the CD group. Swelling and ecchymosis of the affected knee joint, time to straight-leg raising and the range of active knee flexion were improved in the DR group compared with the CD group (all P<0.05).

CONCLUSION:

Compared with temporary clamping drainage, drainage blood reinfusion after total knee arthroplasty can reduce the allogeneic blood transfusion volume and is conducive to early rehabilitation in patients with rheumatoid arthritis.     

Association analysis of anti-Epstein-Barr nuclear antigen-1 antibodies, anti-cyclic citrullinated peptide antibodies, the shared epitope and smoking status in Brazilian patients with rheumatoid arthritis

INTRODUCTION:

Epstein-Barr virus exposure appears to be an environmental trigger for rheumatoid arthritis that interacts with other risk factors. Relationships among anti-cyclic citrullinated peptide antibodies, the shared epitope, and smoking status have been observed in patients with rheumatoid arthritis from different populations.

OBJECTIVE:

To perform an association analysis of anti-Epstein-Barr nuclear antigen-1 antibodies, anti-cyclic citrullinated peptide antibodies, the shared epitope, and smoking status in Brazilian patients with rheumatoid arthritis.

METHODS:

In a case-control study, 140 rheumatoid arthritis patients and 143 healthy volunteers who were matched for age, sex, and ethnicity were recruited. Anti-Epstein-Barr nuclear antigen-1 antibodies and anti-cyclic citrullinated peptide antibodies were examined using an enzyme-linked immunosorbent assay, and shared epitope alleles were identified by genotyping. Smoking information was collected from all subjects. A comparative analysis of anti-Epstein-Barr nuclear antigen-1 antibodies, anti-cyclic citrullinated peptide antibodies, the shared epitope, and smoking status was performed in the patient group. Logistic regression analysis models were used to analyze the risk of rheumatoid arthritis.

RESULTS:

Anti-Epstein-Barr nuclear antigen-1 antibodies were not associated with anti-cyclic citrullinated peptide antibodies, shared epitope alleles, or smoking status. Anti-cyclic citrullinated peptide antibody positivity was significantly higher in smoking patients with shared epitope alleles (OR = 3.82). In a multivariate logistic regression analysis using stepwise selection, only anti-cyclic citrullinated peptide antibodies were found to be independently associated with rheumatoid arthritis (OR = 247.9).

CONCLUSION:

Anti-Epstein-Barr nuclear antigen-1 antibodies did not increase the risk of rheumatoid arthritis and were not associated with the rheumatoid arthritis risk factors studied. Smoking and shared epitope alleles were correlated with anti-cyclic citrullinated peptide-antibody-positive rheumatoid arthritis. Of the risk factors, only anti-cyclic citrullinated peptides antibodies were independently associated with rheumatoid arthritis susceptibility.     

A close association of body cell mass loss with disease activity and disability in Chinese patients with rheumatoid arthritis

OBJECTIVES:

To investigate the association of body cell mass loss with disease activity and disability in rheumatoid arthritis patients.

INTRODUCTION:

Rheumatoid cachexia, defined as the loss of body cell mass, is important but under-recognized and contributes to morbidity and mortality in patients with rheumatoid arthritis.

METHODS:

One hundred forty-nine rheumatoid arthritis patients and 53 healthy, non-rheumatoid arthritis control subjects underwent anthropometric measurements of body mass index and waist and hip circumferences. Bioelectrical impedance analysis was used to determine the subjects'' body compositions, including fat mass, skeletal lean mass, and body cell mass. The disease activity of rheumatoid arthritis was assessed using C-reactive protein serum, the erythrocyte sedimentation rate and the 28-joint disease activity score, while disability was evaluated using a health assessment questionnaire.

RESULTS:

Rheumatoid arthritis patients had lower waist-to-hip ratio (0.86±0.07 vs. 0.95±0.06; p<0.001) and lower skeletal lean mass indexes (14.44±1.52 vs. 15.18±1.35; p = 0.002) than those in the healthy control group. Compared with rheumatoid arthritis patients with higher body cell masses, those with body cell masses lower than median had higher erythrocyte sedimentation rates (40.10±27.33 vs. 25.09±14.85; p<0.001), higher disease activity scores (5.36±3.79 vs. 4.23±1.21; p = 0.022) and greater disability as measured by health assessment questionnaire scores (1.26±0.79 vs. 0.87±0.79; p = 0.004).

CONCLUSIONS:

The loss of body cell mass is associated with higher disease activity and greater disability in rheumatoid arthritis patients. Body composition determined by bioelectrical impedance analysis can provide valuable information for a rheumatologist to more rapidly recognize rheumatoid cachexia in rheumatoid arthritis patients.     

The skin tissue is adversely affected by TNF-alpha blockers in patients with chronic inflammatory arthritis: a 5-year prospective analysis

OBJECTIVE:

We evaluated the incidence of and the main risk factors associated with cutaneous adverse events in patients with chronic inflammatory arthritis following anti-TNF-α therapy.

METHODS:

A total of 257 patients with active arthritis who were taking TNF-α blockers, including 158 patients with rheumatoid arthritis, 87 with ankylosing spondylitis and 12 with psoriatic arthritis, were enrolled in a 5-year prospective analysis. Patients with overlapping or other rheumatic diseases were excluded. Anthropometric, socioeconomic, demographic and clinical data were evaluated, including the Disease Activity Score-28, Bath Ankylosing Spondylitis Disease Activity Index and Psoriasis Area Severity Index. Skin conditions were evaluated by two dermatology experts, and in doubtful cases, skin lesion biopsies were performed. Associations between adverse cutaneous events and clinical, demographic and epidemiological variables were determined using the chi-square test, and logistic regression analyses were performed to identify risk factors. The significance level was set at p<0.05.

RESULTS:

After 60 months of follow-up, 71 adverse events (73.85/1000 patient-years) were observed, of which allergic and immune-mediated phenomena were the most frequent events, followed by infectious conditions involving bacterial (47.1%), parasitic (23.5%), fungal (20.6%) and viral (8.8%) agents.

CONCLUSION:

The skin is significantly affected by adverse reactions resulting from the use of TNF-α blockers, and the main risk factors for cutaneous events were advanced age, female sex, a diagnosis of rheumatoid arthritis, disease activity and the use of infliximab.     

The Clinical Feature of Beh?et's Disease in Northeastern China

Purpose

Behçet''s disease (BD) is a chronic, relapsing, multi-system vasculitis of unknown aetiology with complicated and diversified clinical features predominantly involving oral and genital ulcers, and ocular and cutaneous lesions. The clinical features of this disease have been described to be different according to geographical areas and gender. We investigated the specific clinical features of BD patients in Northeastern China.

Materials and Methods

116 patients involved in this study fulfilled the classification criteria of the International Study Group for BD. The clinical manifestations and results of laboratory tests of BD were recorded in each patient.

Results

The onset was typically between 20-39 years with a slight female predominance. Oral ulcers were the most common manifestation, followed by skin lesions, positive pathergy reaction/genital ulcers, and ocular lesions. Vascular lesion and epididymitis were rare in patients with BD. The frequency of erythema nodosum-like lesion and articular involvement were significantly higher in females, while gastrointestinal involvement was significantly higher in males. The results of laboratory tests showed that the human leukocyte antigen (HLA)-B*51 alleles were positive in 30.9% of patients and the immunological abnormities were present in some patients.

Conclusion

The clinical features of BD showed geographical and gender difference. Genetic and immune factors might participate in aetiopathogenesis of BD.     

Epicardial fat thickness in patients with rheumatoid arthritis

Background

Epidemiologic data indicates that rheumatoid arthritis is an independent risk factor for cardiovascular disease. Epicardial adipose tissue is a novel cardio-metabolic risk factor. Our aim was to evaluate epicardial fat thickness (EFT) using echocardiography in patients with rheumatoid arthritis compared to healthy control subjects. Secondly, we investigated relationship between epicardial fat thickness and clinical and echocardiographic parameters in patients with rheumatoid arthritis.

Method

The study population included 76 consecutive patients with rheumatoid arthritis (64 female; mean age, 53 ±11 years, median disease duration, 7.8 years) and 50 healthy subjects as controls (39 female; mean age, 52 ± 6 years). All patients underwent echocardiography to assess left ventricular diastolic dysfunction, left ventricular hypertrophy and EFT. All values were compared between groups.

Results

EFT was higher in rheumatoid arthritis patients than in healthy controls (0.66±0.20 vs. 0.54±0.18; p= 0.003). Thickness of Intra Ventricular Septum (IVS) (1.1±0.06 and 9.8±0.08; p=0.001) and posterior wall (PW) (0.98±0.05 and 0.93±0.08; p=0.015) was higher in patients with rheumatoid arthritis compared to healthy controls. Early diastolic myocardiac peak velocity or late diastolic mitral peak velocity (E/A) ratio was lower in rheumatoid arthritis patients compared to healthy patients (1.1 ±0.8 and 1.24±0.1 p=0.001) as well as, E/e'' was higher in Rheumatoid arthritis (RA) patients than healthy patients. (E/e'':8.7±1.6 and 8.0±1.4 p=0.020). In patients with rheumatoid arthritis, EFT was positively correlated with hypertension and duration of disease and E/e'' (r: 0.10, p: 0.010, r: 0.306, p: 0.004 and r: 0.465 p: 0.007 respectively) and EFT was negatively correlated with E/A (r: −.262 p:0.022)

Conclusion

To our knowledge, this is the first report about epicardial adipose tissue in rheumatoid arthritis patients. Epicardial fat thickness as an indicator of cardiovascular involvement was higher in rheumatoid arthritis patients.     

Increased risk of depression in patients with rheumatoid arthritis: a seven-year population-based cohort study

OBJECTIVE:

Rheumatoid arthritis (RA) is a costly and crippling autoimmune disease that can lead to the development of depression, contributing to suboptimal clinical outcomes. However, no longitudinal studies have identified an association between rheumatoid arthritis and subsequent depression. This study aimed to investigate the incidence and risk factors of depression among RA patients in Taiwan.

METHODS:

Using Taiwan''s National Health Insurance Research Database, we identified 3,698 newly diagnosed RA patients aged 18 years or older, together with 7,396 subjects without RA matched by sex, age and index date, between 2000 and 2004. The incidence of depression and the risk factors among RA cases were evaluated using Cox proportional-hazard regression.

RESULTS:

The incidence of depression was 1.74-fold greater in the RA cohort than in the non-RA cohort (11.80 versus 6.89 per 1,000 person-years; p<0.01). Multivariate analysis showed that RA subjects who were female, were older, or had comorbidities such as stroke, chronic kidney disease, or cancer had a significantly greater risk of depression compared with those without these conditions.

CONCLUSION:

This population-based cohort study showed a strong relationship between RA and a subsequent risk of depression. The findings could be beneficial to healthcare providers for identifying individuals with a higher predisposition for depression, thereby possibly facilitating the provision of an appropriate rehabilitation intervention after RA onset to support the patient''s adaptation.     

Meta-analysis of the association between HLA-DRB1 allele and rheumatoid arthritis susceptibility in Asian populations

The aims of this study were to summarize results on the association of HLA-DRB1 with rheumatoid arthritis (RA) in Asians and to determine if the shared epitope (SE) hypothesis could explain the meta-analysis results. Among the papers published between January 1987 and July 2006 on RA susceptibility in Asian-Mongoloid populations (Korean, Japanese, Chinese, and Thai), 12 were selected for the metaanalysis. Mongoloid-Asian patients with RA had significantly higher frequencies of HLA-DRB1*0101, *0401, *0410, and *1001 than controls (OR 1.5-2.1, p<0.05 for association). When analyses were restricted to more ethnically homogeneous populations, HLA-DRB1*0405 showed a significant susceptibility to RA in Koreans (OR 5.65, 95% CI 4.32-7.39), whereas the HLA-DRB1*0301, *0403, *0406, *0701, *1301, and *1405 alleles showed protective association with RA (OR 0.32-0.70, p<0.05 for association). In conclusion, it was found that HLA-DRB1 *0101, *0401, *0405, *0410, and *1001 are susceptible, while HLA-DRB1* 0301, *0403, *0406, *0701, *1301, and *1405 are protective in Asian-Mongoloids. All the RA-associated alleles except DRB1*0301 could be explained by the structural model supporting the SE hypothesis that RA susceptibility is determined by the combination of amino acid residues at HLA-DR beta71 and beta74, not by beta71 alone.     

Functional categorization of HLA-DRB1 alleles in rheumatoid arthritis: the protective effect

Because of past recombination event, human leukocyte antigen (HLA) alleles that are not closely related in overall sequence may come to resemble each other in areas coding for peptide binding regions (PBR) of HLA molecules. Peptide binding is likely to be important for the role of HLA molecules in autoimmune disease. As a result, it has been suggested that a strategy of searching for HLA disease associations that groups alleles in functional categories based on PBR motifs may be more successful than conventional strategies based on studying different alleles. Using such functional categorization, we examined the possibility of discriminating subcategories of HLA-DRB1 alleles associated with rheumatoid arthritis (RA) in a Southern French population. HLA-DRB1 genotyping was performed by polymerase chain reaction with sequence-specific oligonucleotide hybridization or sequence-specific primers. HLA-DRB1 alleles were classified according to a functional categorization that defined seven similar subregion structures or restrictive supertype patterns (RSPs) within pocket 4 of HLA-DR peptide binding groove as the molecular basis for grouping these alleles. HLA-DRB1* RSPs "A," "De," "Q," "Dr," "E," " R," and "a" association with susceptibility or resistance to disease was then studied in 200 RA patients versus 200 controls. DRB1* RSP "A" containing the shared epitope alleles (DRB1*0101, *0102, *0401, *0404, *0405, *0408, *1001, *1402; odds ratio [OR] = 4.35; pc < 0.001) had a predisposing effect, with double-dose effect as expected, OR 6.68 (pc < 0.001). Among the six remaining RSPs, two had significantly protective effect: DRB1* RSP "De" (DRB1*0103, *0402, *1102, *1103, *1301, *1302, *1304; OR = 0.33; p(c) < 0.001), and DRB1* RSP "Q" (DRB1*0701; OR = 0.40; pc < 0.001). One had non-significantly protective effect: DRB1* RSP "Dr" (DRB1*08, *1101, *1104, *1106, *12, *1303, *16; OR = 0.68; p < 0.05, pc = not significant [NS]). Three had neutral effect: HLA-DRB1* RSPs "E" (DRB1*0403, *0407, *0901, *1401; OR = 0.71; p = NS), " R" (DRB1*0301, *0302; OR = 0.76; p = NS), and "a" (DRB1*1501, *1502; OR = 0.94; p = NS). The functional categorization allowed us to discriminate among the HLA-DRB1 alleles those that confer a predisposing effect, a neutral effect, and a protective effect in RA.     

Is painless synovitis different from painful synovitis? A controlled,ultrasound, radiographic,clinical trial

OBJECTIVE:

This study compares the clinical, ultrasonography, radiography, and laboratory outcomes of painless and painful chronic synovitis in patients with established rheumatoid arthritis.

METHODS:

This cross-sectional study involved 60 patients with rheumatoid arthritis and synovitis in the metacarpophalangeal joints; 30 of the patients did not experience pain, and 30 had experienced pain for at least 6 months prior to the study. The radiocarpal, distal radioulnar, and metacarpophalangeal joints were evaluated using the ultrasound gray scale, power Doppler, and radiography. Past and present clinical and laboratory findings were also evaluated.

RESULTS:

There were no statistically significant differences between the groups for most of the outcomes. The group with pain scored worse on the disease activity indices (e.g., DAS 28 and SDAI), function questionnaires (HAQ and Cochin), and pinch strength test. A logistic regression analysis revealed that the use of an immunobiological agent was associated with a 3-fold greater chance of belonging to the group that experienced pain. The painless group had worse erosion scores in the second and fifth metacarpophalangeal with odd ratios (ORs) of 6.5 and 3.5, respectively. The painless group had more cartilage with grade 4 damage in the third metacarpophalangeal.

CONCLUSIONS:

The rheumatoid arthritis patients with both painless and painful synovitis exhibited similar disease histories and radiographic and ultrasound findings. However, the ultrasonography evaluation revealed worse scores in the second and fifth metacarpophalangeal of the synovitis patients who did not experience pain.     

Hydroxychloroquine decreases Th17-related cytokines in systemic lupus erythematosus and rheumatoid arthritis patients

OBJECTIVES:

Hydroxychloroquine is an antimalarial agent that has been used in systemic lupus erythematosus and rheumatoid arthritis treatment for many years. Recently, novel mechanisms of action have been proposed, thereby broadening the therapeutic perspective of this medication. The purpose of this study was to evaluate the immunomodulatory activity of hydroxychloroquine in T helper 17 (Th17) cytokines in healthy individuals and patients.

METHODS:

Eighteen female patients with systemic lupus erythematosus (mean age 39.0±12.9 years) and 13 female patients with rheumatoid arthritis (mean age 51.5±7.7 years) were recruited from Universidade Federal de Pernambuco-Brazil. The patients were included after fulfilling four classification criteria for systemic lupus erythematosus or rheumatoid arthritis from the American College of Rheumatology. After being stimulated with phorbol 12-myristate 13-acetate and ionomycin in the absence or presence of different concentrations of hydroxychloroquine, the interleukin 6, 17 and 22 levels were quantified with an enzyme-linked immunosorbent assay in culture supernatants of peripheral blood mononuclear cells from healthy individuals and patients.

RESULTS:

We demonstrated that in peripheral blood mononuclear cells from healthy volunteers and in systemic lupus erythematosus and rheumatoid arthritis patients, there was a significant reduction in the IL-6, IL-17 and IL-22 supernatant levels after adding hydroxychloroquine.

CONCLUSIONS

Our in vitro results demonstrated that hydroxychloroquine inhibits IL-6, IL-17 and IL-22 production and contributes to a better understanding of the mechanism of action of this medication.     

Contrasting diagnosis performance of forced oscillation and spirometry in patients with rheumatoid arthritis and respiratory symptoms

OBJECTIVES:

Pulmonary involvement in rheumatoid arthritis is directly responsible for 10% to 20% of all mortality. The best way to improve the prognosis is early detection and treatment. The forced oscillation technique is easy to perform and offers a detailed exam, which may be helpful in the early detection of respiratory changes. This study was undertaken to (1) evaluate the clinical potential of the forced oscillation technique in the detection of early respiratory alterations in rheumatoid arthritis patients with respiratory complaints and (2) to compare the sensitivity of forced oscillation technique and spirometric parameters.

METHODS:

A total of 40 individuals were analyzed: 20 healthy and 20 with rheumatoid arthritis (90% with respiratory complaints). The clinical usefulness of the parameters was evaluated by investigating the sensibility, the specificity and the area under the receiver operating characteristic curve. ClinicalTrials.gov: NCT01641705.

RESULTS:

The early adverse respiratory effects of rheumatoid arthritis were adequately detected by the forced oscillation technique parameters, and a high accuracy for clinical use was obtained (AUC>0.9, Se = 80%, Sp = 95%). The use of spirometric parameters did not obtain an appropriate accuracy for clinical use. The diagnostic performance of the forced oscillation technique parameters was significantly higher than that of spirometry.

CONCLUSIONS:

The results of the present study provide substantial evidence that the forced oscillation technique can contribute to the easy identification of initial respiratory abnormalities in rheumatoid arthritis patients that are not detectable by spirometric exams. Therefore, we believe that the forced oscillation technique can be used as a complementary exam that may help to improve the treatment of breathing disorders in rheumatoid arthritis patients.     

Genetic polymorphisms at HLA-A, -B, and -DRB1 loci in Han population of Xi'an city in China

Aim

To determine genetic polymorphisms at human leukocyte antigen (HLA)-A, -B, and -DRB1 loci in Han population of Xi’an city in China.

Methods

Polymerase chain reaction-based reverse line-strip sequence specific oligonucleotide hybridization was used to determine the alleles of HLA-A, -B, and -DRB1 in 516 unrelated, healthy individuals of Han population in Xi’an. Allele frequencies at HLA-A, -B, and -DRB1 loci were estimated by direct counting method. Haplotype frequencies were calculated from genotype data by expectation maximization.

Results

A total of 14 alleles of HLA-A, 33 alleles of HLA-B, and 13 alleles of HLA-DRB1 were found. The most common alleles were HLA-A*02 (28.39%), A*11 (19.19%), and A*24 (16.28%); HLA-B*13 (11.05%), B*15 (B62: 9.30%), and B*51 (8.53%); and HLA-DRB1*15 (17.15%), DRB1*09 (13.18%), and DRB1*04 (10.85%). The most common haplotypes of HLA-A-B-DRB1 haplotype were HLA-A*30-B*13-DRB1*07 (3.93%), HLA-A*02-B*46-DRB1*09 (3.20%), and HLA-A*33-B*58-DRB1*17 (1.63%).

Conclusion

The finding that the HLA loci are highly polymorphic in Han population of Xi’an City may be useful for population genetics, HLA-related studies, human identification, and paternity tests in forensic sciences.Human leukocyte antigen (HLA) is a large, closely linked cluster of genes located on chromosome 6p21.3 (1). The HLA system is one of the most polymorphic immunological genetic systems in human genome and usually used in the anthropological analysis, disease linkage analysis, population genetics, forensic sciences, and organ transplantation, especially bone marrow transplantation (2,3). Previous studies have shown that allele and haplotype distribution in the HLA system differ from one ethnic group to another or between the members of the same ethnic group living in different geographic areas. Also, certain alleles are exclusively found in some ethnic groups (4). The comparisons between different populations using genetic distances calculated from HLA allele or haplotype frequencies have been used to determine the genetic relationship between different ethnic groups, so the HLA genetic markers are valuable tools for tracing ancient human migrations and determining the origins of different ethnic groups (5-8). In the present study, we determined the genetic polymorphisms at HLA-A, -B, and -DRB1 loci in a Chinese Han population in Xi’an city and compared them with other neighboring populations.     

Compensatory sweating after restricting or lowering the level of sympathectomy: a systematic review and meta-analysis

OBJECTIVE:

To compare compensatory sweating after lowering or restricting the level of sympathectomy.

METHOD:

A systematic review and meta-analysis were conducted of all randomized controlled trials published in English that compared compensatory sweating after lowering or restricting the level of sympathectomy. The Cochrane collaboration tool was used to assess the risk of bias, and the Mantel-Haenszel odds ratio method was used for the meta-analysis.

RESULTS:

A total of 11 randomized controlled trials were included, including a total of 1079 patients. Five of the randomized controlled trials studied restricting the level of sympathectomy, and the remaining six studied lowering the level of sympathectomy.

CONCLUSIONS:

The compiled randomized controlled trial results published so far in the literature do not support the claims that lowering or restricting the level of sympathetic ablation results in less compensatory sweating.     

Classification of the severity of diabetic neuropathy: a new approach taking uncertainties into account using fuzzy logic

OBJECTIVE:

This study proposes a new approach that considers uncertainty in predicting and quantifying the presence and severity of diabetic peripheral neuropathy.

METHODS:

A rule-based fuzzy expert system was designed by four experts in diabetic neuropathy. The model variables were used to classify neuropathy in diabetic patients, defining it as mild, moderate, or severe. System performance was evaluated by means of the Kappa agreement measure, comparing the results of the model with those generated by the experts in an assessment of 50 patients. Accuracy was evaluated by an ROC curve analysis obtained based on 50 other cases; the results of those clinical assessments were considered to be the gold standard.

RESULTS:

According to the Kappa analysis, the model was in moderate agreement with expert opinions. The ROC analysis (evaluation of accuracy) determined an area under the curve equal to 0.91, demonstrating very good consistency in classifying patients with diabetic neuropathy.

CONCLUSION:

The model efficiently classified diabetic patients with different degrees of neuropathy severity. In addition, the model provides a way to quantify diabetic neuropathy severity and allows a more accurate patient condition assessment.     

Genetic factors and multiple sclerosis in the Moroccan population: A role for HLA class II

Background and objective

Multiple sclerosis (MS) is an autoimmune inflammatory demyelinating disease of the central nervous system that mainly affects young adults. The association between susceptibility to MS and HLA class II genes, in particular the DRB1*15 allele, has been reported in diverse ethnic groups. The aim of our study was to investigate the distribution of HLA-DRB1* and -DQB1* alleles in Moroccan population and their implication in the susceptibility to the disease.

Methods

Fifty-seven MS patients were compared to 172 healthy controls unrelated to one another and matched by age, sex and ethnic origin. HLA class II (DRB1* and DQB1*) typing was performed by PCR-SSP and/or Luminex (PCR-SSO). Allelic and haplotypic frequencies, P-values, odds ratio (OR) and 95% confidence interval (CI) were calculated using the software SPSS.

Results

A significant increase of DRB1*15 allele frequency (17.6% vs 8.4%, OR = 2.67, 95% CI = 1.36–5.23, P = 0.004) and HLA-DRB1*15-DQB1*06 haplotype (8.8% vs 4.08%, OR = 2.78, 95% CI = 1.41–5.48, P = 0.002) were observed in Moroccan MS patients. No association of the DR15 allele with sex or age at onset was appreciated. Concerning HLA-DQB1* alleles, no significant difference between patients and controls was found.

Conclusions

Our results reveal a role for HLA-DRB1*15 allele molecules in the predisposition of Moroccan patients to MS. Although this study should be confirmed on a larger sample size, it analyzes for the first time the possible role of a genetic marker for susceptibility to MS in Moroccan population.     

Increased circulating macrophage migration inhibitory factor levels are associated with coronary artery disease

BACKGROUND:

To evaluate the macrophage migration inhibitory factor and E-selectin levels in patients with acute coronary syndrome.

MATERIALS/METHODS:

We examined the plasma migration inhibitory factor and E-selectin levels in 87 patients who presented with chest pain at our hospital. The patients were classified into two groups according to their cardiac status. Sixty-five patients had acute myocardial infarction, and 22 patients had non-cardiac chest pain (non-coronary disease). We designated the latter group of patients as the control group. The patients who presented with acute myocardial infarction were further divided into two subgroups: ST-elevated myocardial infarction (n = 30) and non-ST elevated myocardial infarction (n = 35).

RESULTS:

We found higher plasma migration inhibitory factor levels in both acute myocardial infarction subgroups than in the control group. However, the E-selectin levels were similar between the acute myocardial infarction and control patients. In addition, we did not find a significant difference in the plasma migration inhibitory factor levels between the ST elevated myocardial infarction and NST-elevated myocardial infarction subgroups.

DISCUSSION:

The circulating concentrations of migration inhibitory factor were significantly increased in acute myocardial infarction patients, whereas the soluble E-selectin levels were similar between acute myocardial infarction patients and control subjects. Our results suggest that migration inhibitory factor may play a role in the atherosclerotic process.