Interleukin (IL)-12, IL-2, and IL-6 gene polymorphisms in Takayasu's arteritis from Turkey

Takayasu's arteritis (TA) is a chronic arterial inflammation of unknown etiology involving mainly the aorta and its major branches. Genetic polymorphisms of cytokines are screened as susceptibility factors for TA in Turkey. A total of 94 patients with TA were investigated for the genetic polymorphisms of the interleukin genes IL12, IL2,and IL6 and were compared with 108 healthy control subjects using polymerase chain reaction-sequence-specific primer method. The frequencies of IL12B 1188 C allele (p = 0.03, OR = 1.7) and CC genotype (p = 0.007, OR = 3.7) were both higher in TA patients than in control subjects. TT genotype at IL2-330 (p = 0.006, OR = 2.4) and GG genotype at IL6-174 (p = 0.04, OR = 1.9) were more frequent in TA patients. Lower prevalence of GT genotype at IL2-330 (p = 0.005, OR = 0.4), CG genotype at IL6-174 (p = 0.001, OR = 0.4), and AG genotypes at IL6-598 (p = 0.01, OR = 0.4) were also detected. The polymorphism of IL-12 as well as IL-6 and IL-2 genes may contribute to susceptibility and pathogenesis of TA by altering cytokine production and inducing inflammation.     

Phenotypic characteristics of B cells in Behçet's disease: increased activity in B cell subsets

OBJECTIVE: Increased numbers of spontaneous Ig secreting B cells and elevated immunoglobulin levels have been described in Beh?et's disease (BD), in addition to changes in numbers and activities of T cells, natural killer cells, and monocyte-macrophages. We investigated other characteristics of B cells in BD. METHODS: B lymphocyte subsets (CD19+CD5+, CD19+CD13+, CD19+CD28+, CD19+CD33+, CD19+CD80+, CD5+CD19+CD45RA+, CD5+CD19+CD45RO+) were phenotypically evaluated in 50 patients with BD, 80 healthy subjects, and 20 other patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and sepsis. RESULTS: Although the B cell number (CD19+) was normal, CD13 and CD33 positive B cells were more numerous in BD and sepsis compared to healthy controls and patients with RA and SLE. The percentage of CD45RO positive B cells was higher in both BD and sepsis, while the percentage of CD80 positive B cells was high only in BD. There was no increase in the CD5+CD19+ B cell subset, previously shown to be increased in several autoimmune diseases. Naive (CD45RA) and memory (CD45RO) status of CD5+CD19+ and CD5-CD19+ B cells showed that CD45RA expression was higher in CD5+CD19+ B cells, whereas expression of both CD45RA and CD45RO was higher in the CD5-CD19+ B cell group compared with healthy controls. CONCLUSION: Although the total B cell number was normal, increased levels of activated and memory B cell subsets suggest a modified B cell function in BD, which may be related to a weak stimulus by an unknown external antigen.     

Lessons from the "Euro-Lupus Cohort"

The "Euro-Lupus Cohort" is composed by 1,000 patients with systemic lupus erythematosus (SLE) that have been followed prospectively since 1991. These patients have been gathered by a European consortium - the "Euro-Lupus Project Group". This consortium was originated as part of the network promoted by the "European Working Party on SLE", a working group created in 1990 in order to promote research in Europe on the different problems related to this disease. The "Euro-Lupus Cohort" provides an updated information on the SLE morbidity and mortality characteristics in the present decade as well as defines several clinical and immunological prognostic factors.     

Mannose binding lectin levels in spondyloarthropathies

OBJECTIVE: Mannose binding lectin (MBL), a member of the collectin family proteins, is a major molecule of the innate immune system; MBL deficiency is associated with increased susceptibility to infections. As gastrointestinal and genitourinary infections are suggested to be among the etiological factors of spondyloarthropathies (SpA), we investigated MBL deficiency in ankylosing spondylitis (AS) and undifferentiated SpA (uSpA). METHODS: One hundred seven patients with AS, 43 patients with uSpA, and 74 healthy controls were studied. Disease activity, radiological scores, and demographic features were recorded. MBL levels were measured with standard ELISA kits. RESULTS: Median MBL levels in AS, uSpA, and controls were 2705 (range 0-5861) ng/ml, 2897 (36-7586) ng/ml, and 3468 (0-7950) ng/ml, respectively. No significant differences were observed in median MBL levels and the prevalence of MBL deficiency between the groups. Bath AS Radiological Index scores were not affected by MBL levels. However, although statistically not significant, radiographic damage quantified by modified Stoke AS Spine Score (mSASSS) was 3 times higher in AS patients with MBL deficiency. Disease activity, clinical picture, and therapies were not associated with MBL levels. CONCLUSION: In AS patients with MBL deficiency, there was a tendency towards a more severe radiographic progression detected by mSASSS.     

Anti-CCP antibodies in rheumatoid arthritis and psoriatic arthritis

Our aim is to assess the prevalence and associated clinical features of anti-CCP (cyclic citrullinated peptide) antibodies for RF (rheumatoid factor)-positive and RF-negative rheumatoid arthritis (RA) and psoriatic arthritis (PsA). In a prospective, cross-sectional, multi-centre study, we determined the titres of anti-CCP antibodies in 208 RA patients (129 RF-positive, 79 RF-negative), 56 PsA patients and 39 healthy controls (HC). Clinical parameters including disease activity (disease activity score 28-DAS28), physical disability (health assessment questionnaire-HAQ), functional capacity (functional class) and radiological erosions were investigated in patients with RA. In PsA patients, clinical and radiological features were determined. Anti-CCP2 antibodies were measured using a second-generation anti-CCP enzyme-linked immunosorbent assay (Euro-Diagnostica, Netherlands). One-hundred four of 129 RF-positive RA (81%), 16 of 79 RF-negative RA (20%), seven of 56 PsA patients (12.5%) and none of the HC had anti-CCP antibodies. RA patients with anti-CCP antibodies had significantly higher disease activity, greater loss of function and more frequent erosive disease than anti-CCP antibody-negative group. In subgroup analysis, anti-CCP antibodies in RF-negative patients were also associated with erosive disease. All PsA patients with anti-CCP antibodies had symmetric arthritis with higher number of swollen joints. The prevalence of anti-CCP antibodies in RF-positive RA patients was significantly higher than in RF-negative RA and PsA patients. Anti-CCP antibodies were also associated with erosive disease in RF-negative RA patients. Both anti-CCP and RF tests were negative in 30% of the patients. Anti-CCP positivity was a frequent finding in PsA and associated with symmetrical polyarthritis.     

Salivary levels of HNP 1–3 are related to oral ulcer activity in Behçet’s disease

Background Saliva contains antimicrobial peptides derived from oral epithelium as well as neutrophils in the innate immune response. The aim of this study was to examine the association between salivary human neutrophil peptide (HNP) 1–3 levels originating from neutrophils and oral ulcers in patients with Behçet’s disease (BD). Methods Ninety‐five patients with BD (F/M: 39/56; mean age: 38.7 ± 11.9 years) and 53 healthy controls (HC; F/M: 23/30; mean age: 35.2 ± 10.1 years) were included in the study. The disease control group (F/M: 20/33; mean age: 33.7 ± 10.7 years) was comprised of patients with oral infection regarding endodontic infection (n = 32) and pericoronitis (n = 21). Salivary HNP 1–3 levels of groups were measured in unstimulated samples by ELISA (Hycult, the Netherlands). Results A statistically significant increase was found in salivary HNP 1–3 levels of patients with BD (2268.28 ± 1216.38 μg/ml) compared with HC (1836.49 ± 857.76 μg/ml), patients with endodontic infection (849.9 ± 376.1 μg/ml), and patients with pericoronitis (824.3 ± 284.02 μg/ml; P = 0.024, 0.000 and 0.000, respectively). The ratio of active oral ulcer (100%, n = 14) was higher in low HNP 1–3 levels (≤1000 μg/ml) than the others (66.7%, n = 54) in active patients with BD (P = 0.008). Moreover, salivary HNP 1–3 levels were significantly lower in patients with endodontic infection and patients with pericoronitis compared with those in the HC group and patients with BD (P = 0.000). Conclusion A decrease in salivary HNP 1–3 levels might be a biological factor for predisposition to oral ulcers in patients with BD and oral infection in healthy patients.     

Early response to immunosuppressive therapy predicts good renal outcome in lupus nephritis: Lessons from long‐term followup of patients in the Euro‐Lupus Nephritis Trial

Objective

In the Euro‐Lupus Nephritis Trial (ELNT), 90 patients with lupus nephritis were randomly assigned to a high‐dose intravenous cyclophosphamide (IV CYC) regimen (6 monthly pulses and 2 quarterly pulses with escalating doses) or a low‐dose IV CYC regimen (6 pulses of 500 mg given at intervals of 2 weeks), each of which was followed by azathioprine (AZA). After a median followup of 41 months, a difference in efficacy between the 2 regimens was not observed. The present analysis was undertaken to extend the followup and to identify prognostic factors.

Methods

Renal function was prospectively assessed quarterly in all 90 patients except 5 who were lost to followup. Survival curves were derived using the Kaplan‐Meier method.

Results

After a median followup of 73 months, there was no significant difference in the cumulative probability of end‐stage renal disease or doubling of the serum creatinine level in patients who received the low‐dose IV CYC regimen versus those who received the high‐dose regimen. At long‐term followup, 18 patients (8 receiving low‐dose and 10 receiving high‐dose treatment) had developed permanent renal impairment and were classified as having poor long‐term renal outcome. We demonstrated by multivariate analysis that early response to therapy at 6 months (defined as a decrease in serum creatinine level and proteinuria <1 gm/24 hours) was the best predictor of good long‐term renal outcome.

Conclusion

Long‐term followup of patients from the ELNT confirms that, in lupus nephritis, a remission‐inducing regimen of low‐dose IV CYC followed by AZA achieves clinical results comparable with those obtained with a high‐dose regimen. Early response to therapy is predictive of good long‐term renal outcome.

     

Anti-Saccharomyces cerevisiae antibodies (ASCA) in spondyloarthropathies: a reassessment

OBJECTIVES: Seronegative spondyloarthropathies, especially ankylosing spondylitis (AS), is shown to be associated with inflammatory bowel disease. Anti-Saccharomyces cerevisiae antibodies (ASCA) is a valid serological marker for Crohn's disease. Presence of ASCA is controversial in AS. In this study, we aimed to investigate the prevalence of ASCA in spondyloarthropathies and its relationship with disease activity and severity. METHODS: One hundred and seventy-five patients with AS, 47 patients with undifferentiated spondyloarthropathy (uSpA) and 103 healthy controls (HCs) were studied. All patients were questioned for demographic features and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) scores. Radiological damage is assessed by Bath Ankylosing Spondylitis Radiology Index (BASRI) and modified Stroke Ankylosing Spondylitis Spinal Score (mSASSS). ASCA levels were measured with standard ELISA kits. RESULTS: There was an overall increased prevalence of ASCA IgA in AS and uSpA compared with HCs (20.6 and 19.1% vs 5.8%, P = 0.0008 and P = 0.02, respectively). No association was observed between ASCA positivity and erythrocyte sedimentation rate, C-reactive protein levels and BASDAI scores. However, ASCA-positive patients had higher BASRI scores [median BASRI: 7 (2-12) vs 6 (2-12); P = 0.037]. Although not reaching significance, they also had reduced chest expansion and higher Bath Ankylosing Spondylitis Functional Index (BASFI) scores. ASCA-positive AS patients also required anti-tumour necrosis factor therapy more frequently (P = 0.006). CONCLUSIONS: ASCA IgA seems to be more prevalent in AS and uSpA. ASCA can also be a marker of radiological damage and a more severe course in AS.