The obesity paradox in ST-segment elevation myocardial infarction patients: A meta-analysis

Objective

The aim of this study was to investigate whether there was a difference in survival after initial percutaneous coronary intervention (PCI) among ST-segment elevation myocardial infarction (STEMI) patients with different body mass index (BMI).

Methods

Literature retrieval was conducted on PubMed, Web of Science, Embase, CNKI, and Wanfang databases to obtain the published studies on the survival of STEMI patients with different BMI after initial PCI from the establishment of the database to 2022. All statistical analyses were performed using STATA16.0.

Results

Two hundred thirty-nine studies were retrieved, and 12 studies were eventually included. Meta-analysis showed that overweight patients [OR = 0.66, 95% CI (0.58, 0.76), p < .001] and obese patients [OR = 0.60, 95% CI (0.51, 0.72), p < .001] had lower in-hospital mortality than healthy-weight patients. Overweight patients [OR = 0.66, 95% CI (0.58, 0.74), p < .001] and obese patients [OR = 0.62, 95% CI (0.53, 0.72), p < .001] had lower short-term mortality than healthy-weight patients. In addition, overweight patients [OR = 0.63, 95% CI (0.58, 0.69), p < .001] and obese patients [OR = 0.59, 95% CI (0.52, 0.66), p < .001] also had lower long-term mortality than healthy-weight patients. There was no significant difference in in-hospital mortality [OR = 1.06, 95% CI (0.89, 1.27), p > .05], short-term mortality [OR = 1.04, 95% CI (0.89, 1.22), p > .05], and long-term mortality [OR = 1.07, 95% CI (0.95, 1.20), p > .05] between overweight and obese patients.

Conclusion

This meta-analysis confirmed an obesity paradox in STEMI patients following PCI. The obesity paradox exists in in-hospital, short-term, and long-term conditions.     

Comparative analysis of the variability of the human leukocyte antigen peptide-binding pockets in patients with acute leukaemia

The association between acute lymphoblastic leukaemia (ALL) and acute myeloid leukaemia (AML) and the human leukocyte antigens (HLA) has rarely been studied in terms of diversity of peptide-binding pockets. The objective of this study was to analyse whether motifs of HLA class I and class II peptide-binding pockets and/or their amino acid positions were differentially associated with ALL and AML. We included 849 patients from the Eurocord/European Blood and Marrow Transplant registry. The HLA peptide-binding pockets whose amino acid variability was analysed were B and F for HLA class I, P4, P6, and P9 for HLA-DRB1, and P4 and P9 for HLA-DQB1. The motif RFDRAY in P4 of HLA-DRB1*16:01/02/03/05 alleles and the motif YYVSY in P9 of HLA-DQB1*05:02/04/05 alleles, were statistically associated with ALL (corrected p value [p_c] = 0.001 and p_c = 0.035 respectively). The frequency of serine 57 in the P9 of HLA-DQB1 was higher in ALL (odds ratio 2.09, 95% confidence interval: 1.27–3.44; p_c = 0.037). Our analysis suggests that specific motifs in terms of HLA class II pockets and amino acids might be unique to ALL. The associations identified in this study encourage further investigation oF the role of HLA peptide-binding pockets and their amino acids in immune processes underpinning acute leukaemia and ultimately in immunotherapy settings.     

The role of human leukocyte antigens as predisposing and/or protective factors in patients with idiopathic thrombotic thrombocytopenic purpura

Fifty-four adult German patients suffering from idiopathic thrombotic thrombocytopenic purpura (TTP) have been examined for HLA class II. All patients presented autoantibodies against ADAMTS13 and ADAMTS13 activity levels <5%. Blood samples have been analyzed for HLA-DRB1 and DQB1 alleles using sequence-specific primer PCR and sequence-specific oligonucleotide PCR. Reference data of German bone marrow and blood donors were obtained from . The results were evaluated employing two-sided binomial tests, and p values were corrected using the Benjamini–Hochberg procedure. A significant accumulation for DQB1*02:02 (p < 0.001) and DRB1*11 (p = 0.003) was found within the patient group. Twenty percent (DQB1*02:02) or 48.1% (DRB1*11) of TTP patients were tested positive for the particular HLA antigen compared to 1.2% (DQB1*02:02) or 23.5% (DRB1*11) in the control group. A tendency for a reduced occurrence of HLA-DRB1*04 was revealed (7.4% in patients compared to 24.6% in controls). An association between the HLA antigens DQB1*02:02 and DRB1*11 and disease susceptibility for idiopathic TTP has been found. A higher risk for disease outbreak within persons carrying the mentioned alleles can be assumed. The reduced occurrence of HLA-DRB1*04 in TTP patients indicates a possible protective effect of this HLA allele in disease development.     

Serodiagnosis of <Emphasis Type="Italic">Mycobacterium avium</Emphasis>-complex pulmonary disease with an enzyme immunoassay kit that detects anti-glycopeptidolipid core antigen IgA antibodies in patients with rheumatoid arthritis

Rheumatoid arthritis (RA) has many pulmonary manifestations, including bronchial abnormalities that can develop into Mycobacterium avium-complex (MAC) pulmonary disease (PD). MAC-PD can be lethal in patients receiving tumor necrosis factor-alpha blockers despite administration of antibiotics. Diagnosis of MAC-PD is often difficult, because MAC is an environmental organism. In this study, we investigated the usefulness of serodiagnosis of MAC-PD in RA patients by using an enzyme immunoassay (EIA) kit that detects anti-glycopeptidolipid (GPL) core antigen IgA antibodies. Antibody levels were measured in 63 patients with RA: 14 with MAC-PD plus 3 cultured nontuberculous mycobacteria (NTM) other than MAC, 16 with pulmonary abnormalities characterizing NTM but undetected in sputum culture, and 30 control subjects. RA patients with MAC-PD showed significantly higher antibody levels than controls (p = 0.02). The cutoff point was set at 0.7 IU/l, making the sensitivity and specificity of the antibody in MAC-PD and control patients 43% and 100%, respectively. The EIA kit is useful for diagnosis of MAC-PD in RA patients because of its high specificity. This test is an easier and less invasive form of examination and could therefore replace bronchoscopy as the main diagnostic procedure for RA patients with MAC-PD.     

In silico calculated affinity of FVIII‐derived peptides for HLA class II alleles predicts inhibitor development in haemophilia A patients with missense mutations in the F8 gene

Forty per cent of haemophilia A (HA) patients have missense mutations in the F8 gene. Yet, all patients with identical mutations are not at the same risk of developing factor VIII (FVIII) inhibitors. In severe HA patients, human leucocyte antigen (HLA) haplotype was identified as a risk factor for onset of FVIII inhibitors. We hypothesized that missense mutations in endogenous FVIII alter the affinity of the mutated peptides for HLA class II, thus skewing FVIII‐specific T‐cell tolerance and increasing the risk that the corresponding wild‐type FVIII‐derived peptides induce an anti‐FVIII immune response during replacement therapy. Here, we investigated whether affinity for HLA class II of wild‐type FVIII‐derived peptides that correspond to missense mutations described in the Haemophilia A Mutation, Structure, Test and Resource database is associated with inhibitor development. We predicted the mean affinity for 10 major HLA class II alleles of wild‐type FVIII‐derived peptides that corresponded to 1456 reported cases of missense mutations. Linear regression analysis confirmed a significant association between the predicted mean peptide affinity and the mutation inhibitory status (P = 0.006). Significance was lost after adjustment on mutation position on FVIII domains. Although analysis of the A1‐A2‐A3‐C1 domains yielded a positive correlation between predicted HLA‐binding affinity and inhibitory status (OR = 0.29 [95% CI: 0.14–0.60] for the high affinity tertile, P = 0.002), the C2 domain‐restricted analysis indicated an inverse correlation (OR = 3.56 [1.10–11.52], P = 0.03). Our data validate the importance of the affinity of FVIII peptides for HLA alleles to the immunogenicity of therapeutic FVIII in patients with missense mutations.     

Decreased Cytokine Production in Patients with Nontuberculous Mycobacterial Lung Disease

Nontuberculous mycobacteria (NTM) are intracellular pathogens that elicit a specific T-cell response characterized by the production of proinflammatory cytokines, including interferon (IFN)-γ, tumor necrosis factor (TNF)-α, and interleukin (IL)-12. However, little information exists regarding the levels of specific cytokines in patients with NTM lung disease. Therefore, we compared cytokine production in peripheral blood mononuclear cells (PBMCs) from patients with NTM lung disease with that in PBMCs from healthy controls. Pro- and anti-inflammatory cytokine production was measured by enzyme-linked immunosorbent assay in the PBMCs of 29 patients with NTM lung disease and 15 healthy controls. Phytohemagglutinin (PHA)-induced IFN-γ production and lipopolysaccharide (LPS)-induced production of TNF-α and IL-12p40 were significantly lower in the PBMCs of patients with NTM lung disease than in those of the healthy controls. The production of these cytokines did not differ significantly between patients infected with Mycobacterium avium complex (MAC) and those infected with Mycobacterium abscessus; however, IL-10 production was lower in patients infected with M. abscessus than in those infected with MAC. Decreased IFN-γ, TNF-α, and IL-12 production may be associated with host susceptibility to the development of MAC and M. abscessus lung disease.     

GWAS identifying HLA‐DPB1 gene variants associated with responsiveness to hepatitis B virus vaccination in Koreans: Independent association of HLA‐DPB1*04:02 possessing rs1042169 G ‐ rs9277355 C ‐ rs9277356 A

Recently, HLA class II loci, including HLA‐DPB1, have been reported to be associated with interindividual variance in the hepatitis B (HB) vaccine response. In this study, we investigated significant single nucleotide polymorphisms (SNPs) for anti‐HBs antibody levels in 6867 healthy Koreans using a genome‐wide association study (GWAS). In GWAS, the top 20 SNPs that showed significant association with anti‐HBs levels (P < 1.0 × 10^?29) all resided in HLA‐DPB1. Utilizing PCR sequencing, we verified the relationship of the top 3 most significant SNPs (rs1042169, rs9277355 and rs9277356) from the GWAS and genotypes of HLA‐DPB1 with the HB vaccine response in Korean infants who received a scheduled vaccination. The DPB1*04:02 allele has G, C and A nucleotides for the 3SNP sites, and was significantly more frequent in responders than in nonresponders (10.9% vs 1.0%, P_c = 0.018). DPB1*05:01 was significantly more frequent in nonresponders than in responders (49.0% vs 31.1%, P_c = 0.018). In multivariate logistic regression, DPB1*04:02 showed a significant association with both vaccine response (P = 0.037, OR = 8.465) and high‐titre response (P = 0.027, OR = 9.860). The haplotypes rs1042169 G ‐ rs9277355 C ‐ rs9277356 A showed a significant association with a high‐titre response only (P = 0.002, OR = 2.941). In conclusion, DPB1*04:02 possessing rs1042169 G ‐ rs9277355 C ‐ rs9277356 A is an independent predictor of the HB vaccine response in Koreans.     

Unveiling axial involvement in psoriatic arthritis: An ancillary analysis of the ASAS-perSpA study

ObjectiveTo determine the clinical profile of axial psoriatic arthritis (PsA) in a worldwide setting. Secondly, to identify factors associated with the development of axial involvement in patients with PsA.MethodsData from 3684 patients with axial spondyloarthritis (axSpA) or PsA from the ASAS-perSpA study were analysed. The ASAS-perSpA is a cross-sectional study that recruited consecutive patients with SpA (as diagnosed by their rheumatologist) from 68 centers worldwide and collected patient and disease data. First, 2651 axSpA patients and 367 PsA patients with any history of axial involvement (axPsA) were compared using logistic regression to later identify predictive factors for rheumatologist diagnosis of axPsA. Secondly, 367 axPsA patients were compared with 666 PsA patients lacking axial involvement (peripheral PsA [pPsA]) and the characteristics associated with axial manifestations were explored by logistic regression analysis.ResultsPatients with axPsA were older and less frequently males or HLA*B27 positive in comparison with axSpA patients. Additionally, while patients with axPsA had more peripheral manifestations and psoriasis, other extra-musculoskeletal manifestations (IBD and uveitis) were more frequent in those with axSpA. In the multivariable analysis, older age at diagnosis (OR = 1.04), peripheral arthritis (OR = 7.32) and dactylitis (OR = 2.82) were significantly associated with the diagnosis of axPsA. However, uveitis (OR = 0.22), IBD (OR = 0.12), HLA*B27 carriership (OR = 0.26) or sacroiliitis on imaging (OR = 0.5) were inversely associated with axPsA diagnosis as compared to axSpA. Axial involvement in patients with PsA was significantly associated with male gender (OR = 1.68), elevated CRP (OR = 2.87) and the absence of psoriasis (OR = 0.33).ConclusionIn this worldwide setting axPsA was defined by rheumatologists as a unique phenotype, with disease features lying between axSpA and pure pPsA.     

D6S265*15 marks a DRB1*15, DQB1*0602 haplotype associated with attenuated protection from type 1 diabetes mellitus

Aims/hypothesis The HLA class II DQB1*0602 allele confers strong dominant protection against type 1 diabetes but protection is not absolute. The aim of this study was to identify markers within the HLA region that differentiate DQB1*0602 haplotypes and show different associations with disease risk. Methods We defined alleles at eight microsatellite markers spanning the HLA region in a case-control cohort from Sweden. Results We found that allele 15 at marker D6S265 (109 kb centromeric of HLA-A) was over-represented among patients carrying DRB1*15, DQB1*0602. A detailed haplotype analysis showed that DRB1*15, DQB1*0602 haplotypes carrying D6S265*15 have a ten-fold higher odds ratio (OR) than those carrying other alleles and thus confer reduced protection [OR D6S265*15=0.186 (95% CI 0.074, 0.472) vs OR D6S265*15−=0.017 (95% CI 0.005, 0.062), p<0.001]. Conclusions/interpretation Our data support the existence of a locus that modifies the protective effect associated with DQB1*0602. Typing for allele D6S265*15 can identify a less protective DQB1*0602 haplotype, thereby allowing a more accurate prediction of type 1 diabetes risk. Electronic Supplementary Material Supplementary material is available for this article at * For full lists of members of these study groups, see Electronic Supplementary Material.     

Distribution of HLA-B27 and its alleles in patients with reactive arthritis and with ankylosing spondylitis in Tunisia

The purpose of the present study is to investigate the frequency of HLA-B27 and its alleles in reactive arthritis (ReA) and in ankylosing spondylitis (AS) in Tunisia. HLA-B27 alleles were typed by PCR amplification with sequence-specific primers. We studied 17 patients with ReA associated with urethritis or with gastrointestinal infection; 42 HLA-B27-positive patients with AS and 100 healthy controls. Eleven ReA patients (67.7%) were HLA-B27 positive. There was an increased frequencies of HLA-B27 (P = 7.76 × 10⁻¹², OR = 59.30) and a moderate increase of HLA-B51 (P = 0.015; OR = 4.91) alleles in ReA patients when compared with healthy controls. Four B27 subtypes were identified: B*2702, 05, 09 and B*2712. The distribution of these alleles in the ReA patients was 37.5% for B*2702 and B*2705. Only these two subtypes were detected in 18 (42.8%) and 24 (57.1%), respectively, of the AS patients. B*2709 and B*2712 were relatively rare in ReA patients and were identified in one case each. Our results showed a restricted number of HLA-B27 subtypes associated with ReA and AS. B*2702 and 2705 were common in ReA and AS patients.     

HLA class 1 associations in Henoch Schonlein purpura: increased and decreased frequencies

Henoch Schonlein purpura (HSP) is the most common vasculitis of childhood. Susceptibility to HSP and associated clinical heterogeneity in HSP may be conferred by a number of genetic loci, including the major histocompatibility complex. We aimed to investigate the implications of the human leukocyte antigen (HLA) class 1 alleles in susceptibility to HSP and determine the possible associations with renal, gastrointestinal (GI), and joint manifestations of the disease. 110 children with HSP (66 boys, 44 girls) and 250 unrelated healthy controls were enrolled in the study. The mean age was 8.65 ± 3.59 years. HSP was diagnosed on the basis of clinical and laboratory data according to the American College of Rheumatology classification. The diagnosis was supported with skin and/or kidney in most of the patients. Clinical and laboratory findings revealed: skin involvement in 110 (100%), joint manifestations in 82 (74.5%), GI symptoms in 58 (52.7%), and hematuria and/or proteinuria in 36 (32.7%) patients. HLA class 1 alleles were identified by DNA amplification, hybridized with specific primer sequences. Comparison of frequencies between patients and controls were made by using the Fisher’s exact test. Odds ratio (OR) was used as the measure of association. HLA A2, A11, and B35 antigens showed an increased risk for predisposition to HSP (OR = 1.714, 95%CI = 1.088–2.700, p = 0.020; OR = 2.185, 95%CI = 1.289–3.703, p = 0.003; and OR = 2.292, 95%CI = 1.451–3.619, p = 0.000, respectively), while HLA A1, B49, and B50 antigens revealed decreased risk for predisposition to HSP (OR = 4.739, 95%CI = 1.828–12.345, p = 0.001; OR = 3.268, 95%CI = 0.955–11.236, p = 0.047; and OR = 7.462, 95%CI = 0.975–55.555, p = 0.024, respectively). Considering the renal involvement and severity of proteinuria, there was no association with HLA class 1 alleles. Our results suggest that the increased frequency of HLA A2, A11, and B35 alleles in unselected pediatric HSP patient population and miscarrying of HLA A1, B49, and B50 could be considered as a risk factor for susceptibility to HSP.     

Human leucocyte antigen‐B27 subtypes in Korean patients with ankylosing spondylitis: higher B*2705 in the patient group

Aim: To investigate the distribution of human leucocyte antigen (HLA) class I antigens and B27 subtypings in a group of B27(+) ankylosing spondylitis (AS) patients and a group of B27(+) control individuals, and to compare differences in their clinical features using subtyping. Methods: At otal of 143 B27(+) AS samples and 32 B27(+) control samples were collected consecutively from two rheumatology centres in South Korea. All patients were diagnosed according to the modified New York criteria for AS. Medical records of the patients were retrospectively reviewed for demographic information, Bath disease activity index (BASDAI) scores, laboratory parameters at diagnosis and extra‐articular manifestations. Polymerase chain reaction‐sequence‐specific primer typing for the B27 subtypes was performed using the Dynal HLA‐B27 high resolution kit. Results: Whereas subtypes in Korean AS patients include B*2704 (n = 11, 7.7%) B*2705 (n = 130, 90.9%), and B*2710 (n = 2, 1.4%), those of the control groups include B*2704 (n = 11, 34.4%), B*2705 (n = 19, 59.4%), B*2710 (n = 1, 3.1%), and B*2715 (n = 1, 3.1%). The proportion of B*2705 subtypes were significantly higher in the AS group than the control group (P < 0.01). There were no differences in clinical features (peripheral arthritis, uveitis, BASDAI scores) or laboratory parameters between the two groups. Conclusion: In Korean AS patients, not in the control group, the HLA‐B*2705 subtype was higher than other subtypes, in contrast to AS patients from Japan and China. B27 subtypes in AS patients were not associated with clinical features or laboratory parameters.     

HLA class I and II polymorphisms in Mexican Mestizo patients with dengue fever

Host genetics in dengue hemorrhagic fever (DHF) pathophysiology has not been extensively investigated. Most studies have focused on HLA in different populations; however these reported associations have not been replicated. We performed a case-control study to analyze possible associations of HLA-A, HLA-B, HLA-Cw, HLA-DRB1 and HLA-DQB1 alleles with clinical disease severity caused by dengue virus infection. Our population consisted of 39 individuals (DF: 23, DHF: 16) and 34 healthy controls from the State of Morelos, Mexico. HLA loci were genotyped by nucleotide sequencing method. Statistical analyses revealed associations in three alleles: HLA-B*35 was negatively associated with symptomatic disease (p < 1 × 10⁻⁴, p_c = 0.01, OR = 0.12, 95%CI = 0.037-0.39), and DF (p = 0.0007, p_c = 0.03, OR = 0.13, 95%CI = 0.031-0.51). HLA-DQB1*0302 was positively associated with DHF (p = 0.018, p_c = NS, OR = 5.02, 95%CI = 1.05-25.34), and negatively with DF (p = 0.011, p_c = NS, OR = 0.23, 95%CI = 0.06-0.84). HLA-DQB1*0202 was positively associated with DF only (p = 0.012, p_c = NS, OR = 7.0, 95%CI = 1.11-73.8). We identified possible associations of HLA-B and HLA-DQB1 alleles with the risk of developing symptomatic disease, DF and DHF in a Mexican Mestizo population.     

Nontuberculous Mycobacterial Lung Infections in Ontario, Canada: Clinical and Microbiological Characteristics

Study Objectives The aim of this study was to determine gender and clinical phenotype frequencies in pulmonary nontuberculous mycobacterial (NTM) infection and the frequency of disease in NTM isolates. Design The study is a retrospective observational cohort study of two overlapping cohorts: population cohort and clinical cohort. Setting The study was conducted at the University Health Network and Ontario Mycobacteriology Laboratory in Toronto, Ontario, Canada. Patients or Participants The population cohort consisted of all patients with one or more pulmonary NTM isolates in Ontario in 2003. The clinical cohort consisted of all patients with one or more pulmonary NTM isolates at our hospital in 2002–2003. Interventions The study entailed the review of laboratory records and demographics (both cohorts) and detailed clinical records (clinical cohort). Measurements and Results In the population cohort (N = 1651), females comprised 48% overall and 51% with microbiological disease criteria. In the clinical cohort (N = 552), females comprised 48% overall and 55% with NTM disease. In the population cohort, 45% fulfilled microbiological disease criteria, and in the clinical cohort 46% of patients had disease. Patients with MAC isolates fulfilled microbiological disease criteria in 51% of population cohort cases and all disease criteria in 52% of clinical cohort cases. Women more commonly fulfilled microbiological disease criteria in the population cohort (51 vs. 45%, P = 0.02) and all disease criteria in the clinical cohort (53 vs. 40%, P = 0.03). Among clinical cohort patients, 26% (13 women, 44 men) had fibrocavitation, while 62% (101 women, 37 men) had nodular bronchiectasis. Conclusions Women comprised a small majority with disease. Nodular bronchiectasis in women was most common, but significant proportions of each gender with each radiographic type were observed. NTM isolation, particularly MAC, was frequently associated with disease.     

HLA-DRB1 Alleles are Associated With COPD in a Latin American Admixed Population

IntroductionWhile the molecular mechanisms of COPD pathogenesis remain obscure, there is mounting evidence supporting a key role for autoimmunity. Although human leukocyte antigens (HLA) alleles have been repeatedly associated with autoimmune processes, the relation between HLA and COPD remains largely unexplored, especially in Latin American (LA) populations. Consequently, this study aimed to investigate the presence of HLA class I and II alleles in COPD patients and healthy controls in a LA population with admixed ancestry.MethodsCOPD patients (n = 214) and age-matched controls (n = 193) were genotyped using the Illumina Infinium Global Screening Array. The classic HLA alleles were imputed using HLA Genotype Imputation with Attribute Bagging (HIBAG) and the Hispanic reference panel. Finally, the distribution of HLA-DRB1 alleles was reexamined in 510 randomly recruited unrelated volunteers.ResultsCODP patients showed a higher HLA-DRB1*01:02 allele frequency (6.54%) than healthy controls (3.27%, p = 0.04, OR = 2.07). HLA-DRB1*01:02 was also significantly associated with FEV₁ (p = 0.04) and oxygen saturation (p = 0.02), and the FEV₁/FVC ratio was higher in HLA-DRB1*15:01-positive patients (p = 9 × 10⁻³).ConclusionWe report an association among HLA-DRB1 alleles, COPD risk and pulmonary function parameters for the first time in Latin Americans. Since HLA-DRB1 genetic variability relates to the individual autoimmune response, these results support a role of autoimmunity in the pathogenesis of COPD.     

A three-way interplay of DR4, autoantibodies and synovitis in biopsy-proven idiopathic inflammatory myositis

The aim of this study was to determine the HLA and autoantibody associations of patients with histologically confirmed idiopathic inflammatory myositis (IIM). Serum and DNA were archived from South Australian patients with biopsy-proven dermatomyositis (DM), polymyositis (PM) and inclusion body myositis (IBM). HLA typing for Class I and II alleles was performed by serology and DNA-based technology, respectively, for 133 myositis patients and 166 Caucasian population-based controls. Myositis-specific and myositis-associated autoantibodies were detected by line immunoblot. All alleles of the 8.1AH were associated with myositis susceptibility. The B8-DR3 haplotype fragment conferred the strongest susceptibility (OR 2.9, 95% CI 1.8–4.6), and the B-DR region of other ancestral haplotypes was associated with myositis subgroups. Autoantibodies were present in 42/130 (32%) IIM patients and were more frequent in DM (11/17, 65%) than PM (23/70, 33%) or IBM (8/43, 19%), P = 0.002. Autoantibodies were associated with DRB1*03 (P = 0.0005) but also with DRB1*04 (P = 0.004). The frequency of autoantibodies in the three myositis subgroups mirrored the frequency of DR4. Polyarthralgia (±synovitis) was more common in DM/PM (30/76, 39%) than IBM (3/32, 9%), P = 0.004, and there was a strong ordinal association between the prevalence of autoantibodies and polyarthralgia ± synovitis (proportional OR = 5.5, 95% CI 2.3–13.7, P = 0.0004). The central MHC region confers the strongest susceptibility for IIM and also modulates disease phenotype. Our findings reveal a novel association of autoantibodies with DR4 and with arthralgia/synovitis in IIM and raise the possibility of a genetically (DR4) determined citrullination of myositis autoantigens expressed in muscle and synovium.     

Giardia intestinalis genotypes: Risk factors and correlation with clinical symptoms

This study was conducted to identify genotypes related risk factors of Giardia intestinalis in an Orang Asli (aboriginal) community in Pahang, Malaysia. Stool samples were collected from 321 individuals aged between 2 and 76 years old, of whom 160 were males and 161 were females. Faecal samples were processed with trichrome staining technique for the primary identification of G. intestinalis. Molecular identification was carried out by the amplification of a partial SSU rRNA gene using nested PCR. PCR products were purified and genotyped. 42 samples successfully amplified from the 76 positive faecal samples, only 1 was Assemblage A, the rest were Assemblage B. Risk analysis based on the detected genotypes of Giardia using univariate analysis and logistic regression identified three significant risk factors of giardiasis caused by assemblage B which included children ≤12 years (OR = 13.56, 95% CI = 1.79–102.64, p = 0.012), females (OR = 2.52, 95% CI = 1.11–5.75, p = 0.027) and eating fresh fruits (OR = 7.78, 95% CI = 1.01–60.00, p = 0.049). Assemblage B infection was significantly correlated with clinical symptoms of giardiasis (OR = 2.4, 95% CI = 1.13–5.12, p = 0.019). Females infected with Assemblage B were at higher risk of manifesting gastroenteritis signs and symptoms (OR = 3.9, 95% CI = 1.50–10.31, p = 0.004). It has been concluded that giardiasis is still a public health problem in Orang Asli community and most commonly caused by assemblage B. The dynamic of transmission is most probably anthroponotic which is human to human either directly or indirectly through contaminated food. This route of transmission should be considered in the control strategy of the disease. Mass treatment together with health education could be the most practical intervention for reducing the infection. Those at high risk should receive more attention from public health authorities.     

Molecular typing of HLA-class II alleles reveals an association with autoantibodies and disease subsets of systemic sclerosis in a North Indian (Kashmir) population

Aim of the workTo identify specific human leukocyte antigen (HLA)-Class II (DRB/DQB1/DPB1) alleles associated with systemic sclerosis (SSc) and to explore their relation with SSc autoantibodies, clinical manifestations, and disease subsets.Patients and methodsHLA-class II alleles (DRB1/DRB3/DRB4/DRB5/DQB1) were determined by DNA typing in 80 SSc cases and 60 matched controls and HLA-DPB1 in 40 SSc patients and 30 controls by allele-specific-polymerase chain reaction with sequence-specific primers (PCR-SSP).ResultsThe mean age of SSc patients was 36.9 ± 9.4 years; 76 females and 4 males (F:M 19:1) and a disease duration of 5.3 ± 3.3 years, they were 43(53.7%) limited and 37(46.2%) diffuse subtypes. SSc was significantly associated with DRB1*11, DRB1*01, DQB1*04, and DQB1*03*03 in a >4-fold manner, whereas DPB1*04 had a >7-fold increased risk compared to controls. There was a strong association between DRB1*11 (p = 0.04), DQB1*03*03 (p = 0.005), and DPB1*13 (p = 0.009) with anti-topoisomerase I (anti-topoI) whereas the frequency of DRB1*01 (p < 0.0001) was increased in patients with anti-centromere (ACA) positive SSc compared those negative (56% vs 25%; p < 0.0001). DRB1*03, DRB1*15, and DQB1*03*01 were SSc protective alleles in patients with positive ACA. Anti-topo I was associated with interstitial lung disease (ILD) (p < 0.01), whereas ACA with pulmonary arterial hypertension (PAH) (p = 0.01) and protection against ILD (p < 0.001). In addition, HLA-DRB1*03, DQB1*03*01and DPB1*03 were more frequent in patients with ILD than in patients without.ConclusionAssociations between specific HLA-class II alleles with certain SSc-specific autoantibodies (anti-topo I and ACA) were identified. Specific HLA associations with clinical and serological subtypes could serve as biomarkers of disease severity and progression in SSc.     

Molecular analysis of Mycobacterium tuberculosis from tuberculous meningitis patients in Thailand

The first retrospective molecular characterization of Mycobacterium tuberculosis from cerebrospinal fluid of 158 tuberculous meningitis (TBM) in Thailand, collected between 1995 and 2005, was performed by Southern-blot hybridization with an IS6110 probe and spoligotyping on 152 and 147 isolates, respectively. Antituberculous drug susceptibility testing was performed in 149 patients, 118 of whom (79.2%) contained pan-sensitive strains and eight (5.4%) harbored multidrug-resistant M. tuberculosis. IS6110 RFLP typing revealed 110 RFLP patterns with 57.9% of patients infected with the Beijing genotype. This percentage was significantly higher than that in a previous report from pulmonary tuberculosis patients. Fifteen of 18 TBM patients (83%) aged <15 years were infected with Beijing isolates (OR = 4.47, p = 0.018). There were 40 spoligotypes, with 118 patients (80.3%) being clustered. The biggest cluster, which consisted of 84 patients, was the Beijing spoligotype (57.1%). There were 16 novel spoligotypes from 16 patients compared to the Fourth International Spoligotyping Database, SpolDB4. Sixty-four percent of the patients were male, and the mean age of patients was 33.8 years. Beijing isolates from 2001 to 2005 were found in higher percentages than those from 1995 to 2000, but this difference was not significant (p = 0.28).     

Polymorphism of glutathione S-transferase Omega gene: association with risk of childhood acute lymphoblastic leukemia

Purpose  To evaluate the association between glutathione S-transferase Omega (GSTO) genes polymorphism and the susceptibility of acute lymphoblast leukemia (ALL). Methods  The polymorphism of GSTO1 and GSTO2 genes were analyzed in 99 ALL patients compared with 100 healthy children by PCR-based restriction fragment length polymorphism (RFLP) analysis. Results   GSTO1*A140D polymorphism was significantly associated with susceptibility to ALL (OR = 2.24, 95% CI = 1.16–4.35, P = 0.009) whereas, GSTO2*N142D genotype was significantly interacted with high risk group of childhood ALL (OR = 5.52, 95% CI = 1.72–17.71, P = 0.004). Conclusion  This study revealed gene polymorphism in glutathione S-transferase Omega class may be a risk factor to the development of acute childhood lymphoblastic leukemia.