Association of anti-cyclic citrullinated peptide antibodies and rheumatoid factor isotypes with HLA-DRB1 shared epitope alleles in Egyptian rheumatoid arthritis patients.

INTRODUCTION: The most common genetic risk factor for rheumatoid arthritis (RA) is human leucocyte antigen DRB1 (HLA-DRB1) shared epitope (SE). AIM: To investigate the relationship between anti-cyclic citrullinated peptide (anti-CCP), rheumatoid factor (RF), immunoglobulin (Ig)G, IgM and IgA and HLA-DRB1 SE among Egyptian patients with RA. METHODS: Serum levels of anti-CCP antibodies and RFIgG, RFIgM, RFIgA were assayed using enzyme-linked immunosorbent assay for 157 Egyptian RA patients and 150 healthy controls attending the outpatient clinics of National Research Center and Kasr El Aini Hospital. HLA-DRB1 genotyping was performed by the DynalAllSetTM polymerase chain reaction (PCR) single specific primer low-resolution typing kits. Amplified PCR product was checked using 3% agarose gel. RESULTS: HLA-DRB1-SE was found among 129 (82.2%) RA patients and 67 (44.7%) controls (odds ratio [OR] 5.7, CI 3.4-9.6, P < .0001). The risk of RA development was higher with the presence of SE two alleles (OR 11.6, P < .0001), while the OR for 1 copy SE allele was 4.4 (P < .0001). HLA-DRB1-SE was significantly associated with positive as well as negative anti-CCP and RF isotypes. The stronger association was with anti-CCP positivity with OR 11 (5.1-23.6), P < .0001. Furthermore, the risk of development of positive anti-CCP and RF isotypes was higher with the presence of 2 copies of SE alleles than with 1 copy. CONCLUSION: The prevalence of HLA-DRB1-SE is high in Egyptian RA patients. The role of SE in RA patients is most probably related to the development of anti-CCP positive RA rather than the development of anti-CCP positivity.

Pulmonary manifestations in a group of patients with Behcet's disease.

AIM: In this study we investigated the frequency and characteristics of pulmonary manifestations in a group of patients with Behcet's disease (BD) who were admitted to Cairo University Hospital. METHODS: Fifteen patients were included in our study, 14 men (93.3%) and one woman (6.66%).Their mean age was 30.06 ± 9.8 years and the mean age of onset of BD was 23.7 ± 5.54 years. All patients were subjected to full history taking, clinical examination, plain chest X-ray and helical computed tomography (CT) study of the chest. RESULTS: Pulmonary involvements were detected in 11 patients with BD, 73.3% of cases: 10 men (90.9%) and one woman (9.09%).Their mean age was 28.8 ± 8.07, the mean age of onset of BD was 23.2 ± 5.59 years and the mean disease duration until lung manifestations appear was 3.7 ± 4.8 years. The main pulmonary and constitutional symptoms in these 11 patients were as follows: dyspnea 81.8%, cough 63.6%, weight loss 63.6%, chest tightness 54.5%, hemoptysis 45%, massive hemoptysis 27.2%, fever 36.3% and expectoration 36.3. Analysis of both vascular and parenchymal lung lesions in helical CT scan in the 11 patients with BD were as follows: pulmonary artery aneurysm (PAA) occurred in 5/11 patients (45.4%), pulmonary nodules occurred in 3/11 patients (27.2%), pleural effusion occurred in 3/11 patients (27.2%), pulmonary embolism and infarction occurred in 1/11 patients (9.09%) and pneumonitis occurred in 1/11 patients (9.09%). CONCLUSION: The higher frequency of pulmonary manifestations in our patients (73.3%) and the higher frequency of PAA (33.3%) could be related to the fact that this study was conducted on a group of patients who were admitted to the hospital with more severe illnesses.

Association of PTPN22 1858C→T polymorphism, HLA-DRB1 shared epitope and autoantibodies with rheumatoid arthritis.

To assess impact of PTPN22 1858C→T polymorphism, HLA shared epitope and autoantibodies on susceptibility and severity of rheumatoid arthritis (RA). A total of 150 RA patients and 150 controls were included in the study. Anti-cyclic citrullinated peptide (anti-CCP) and rheumatoid factor isotypes (IgG, IgM and IgA) were assayed by ELISA. PTPN22 1858C→T polymorphism was performed by RFLP analysis and HLA-DRB1 genotyping by PCR-SSP analysis. Single-view, anteroposterior radiographs of the hands and feet were obtained on all RA patients. The results showed association of PTPN22 1858 T allele with RA (OR = 2.3, 95 % CI 1.5-3.5) and bone erosion (OR = 2.9, 95 % CI 1.1-7.6). The associations increased with the combination of positive autoantibodies, HLA-DRB1 SE with PTPN22 1858 T allele carriage. The highest association was with the combination with anti-CCP antibodies (OR = 47.3, 95 % CI 10.9-204.4 for RA and OR = 69.4, 95 % CI 15.8-305.5 for erosion p < 0.001). Combination of PTPN22 1858 T allele carriage with negative RF isotypes or with absence HLA-DRB1 SE showed no significant association with RA. The presence of PTPN22 1858C→T polymorphism with HLA SE and autoantibodies increases risk of RA development and erosive disease.

Validation of the classification criteria for cryoglobulinaemic vasculitis.

OBJECTIVE: The aim of this study was to validate the classification criteria for cryoglobulinaemic vasculitis (CV). METHODS: Twenty-three centres were involved. New patients with CV (group A) and controls, i.e. subjects with serum cryoglobulins but lacking CV based on the gold standard of clinical judgment (group B) and subjects without cryoglobulins but with clinical features that can be observed in the course of CV (group C), were studied. Positivity of serum cryoglobulins was necessary for CV classification. Sensitivity and specificity of the criteria were calculated by comparing group A vs group B. The group A vs group C comparison was done to demonstrate the possible diagnostic utility of the criteria. RESULTS: The study included 268 patients in group A, 182 controls in group B and 193 controls in group C (small vessel vasculitis, 51.8%). The questionnaire (at least 2/3 positive answers) showed 89.0% sensitivity and 93.4% specificity; the clinical item (at least 3/4 clinical involvement) showed 75.7% sensitivity and 89.0% specificity and the laboratory item (at least 2/3 laboratory data) showed 80.2% sensitivity and 62.4% specificity. The sensitivity and specificity of the classification criteria (at least 2/3 positive items) were 89.9% and 93.5%, respectively. The comparison of group A with group C demonstrated the clinical utility of the criteria in differentiating CV from CV mimickers. CONCLUSION: Classification criteria for CV were validated in a second, large, international study confirming good sensitivity and specificity in a complex systemic disease.

Expression of TNF-α, APRIL and BCMA in Behcet's disease.

BACKGROUND: Tumor necrosis factor-alpha (TNF-α) is an important proinflammatory cytokine which plays an important role in the immunopathogenesis of Behcet's disease (BD). B cell activating factor (BAFF) and its homolog A proliferation inducing ligand (APRIL) are members of the tumor necrosis factor family. BAFF binds to 3 receptors, B cell activating factor receptor (BAFF-R), transmembrane activator and calcium modulator ligand interactor (TACI), and B cell maturation antigen (BCMA) that are expressed by B cells. OBJECTIVE: Estimation of the serum levels of TNF-α, APRIL, BAFF, and BCMA in patients with BD in an effort to evaluate their degree of involvement in the pathogenesis and development of BD. PATIENTS AND METHODS: This study included 30 male patients fulfilling the international study group criteria for the diagnosis of BD. Twenty age-matched healthy male volunteers served as control. Serum samples were used for quantification of TNF-α, APRIL, BCMA, BAFF, and hsCRP using ELISA techniques. RESULTS: The mean serum levels of TNF-α, APRIL, BCMA, and BAFF were more elevated in cases than in controls in a statistically significant manner (P < 0.001). Positive correlation was observed between hs-CRP and BDCAF (Behcet's disease current activity forum) index (r 0.68, P < 0.001). None of the TNF family members tested was affected by a positive pathergy test. CONCLUSIONS: Patients have significantly higher levels of TNF family members' (TNF-α, BAFF, APRIL, and BCMA) compared to controls which might contribute to the pathogenesis of BD.

Anti-cyclic citrullinated peptide antibodies as a discriminating marker between rheumatoid arthritis and chronic hepatitis C-related polyarthropathy.

Articular involvement is a frequent extrahepatic manifestation of hepatitis C virus (HCV) infection. The distinction between HCV-related polyarthropathy and true RA may be very difficult, especially with recent onset RA before articular damage and erosions develop. The objective of the study is to assess the diagnostic utility of anti-CCP antibodies and compare it with that of rheumatoid factor (RF) in distinguishing between rheumatoid arthritis (RA) and HCV-related polyarthropathy. Anti-cyclic citrullinated peptide (CCP) antibodies and RF were determined in the sera of 30 patients with RA and 22 patients with HCV-related polyarthropathy. Anti-CCP antibodies were positive in 83.3% of patients with RA and in 4.5% in patients with HCV and polyarthropathy. RF was positive in 90% of RA patients and in 81.1% of HCV patients with polyarthropathy. The anti-CCP antibodies showed higher specificity for RA compared with RF (95.4 vs. 18.2%). However, the sensitivity of anti-CCP was comparable to that of RF (83.3 vs. 90%). In conclusions, anti-CCP antibodies are reliable laboratory markers to differentiate between RA and HCV-related polyarthropathy.

Clinical features of Behcet's disease in Egypt.

Behcet's disease (BD) is a chronic relapsing multisystem disease of unknown etiology. Ethnic origin is one of the factors that may modulate the prevalence and the expression of BD. To study the clinical characteristics of Egyptian patients with BD, and compare the pattern of the disease in Egyptians with studies from other countries. Sixty-three patients with BD were studied over a 4-year period. A rheumatologist, dermatologist, neurologist and other specialists as indicated assessed the patients clinically. Laboratory and radiological examinations were done to confirm the diagnosis to rule out any condition that may mimic BD. Sixty-one patients were men, two were women, the mean age of the patients was: 32.8 +/- 8.3 years, age of onset of the disease varied between 17 and 37.4 years. The initial presenting manifestation was oral ulcers in 39.7% of patients, followed by orogenital ulcers in 23.8%, followed by deep venous thrombosis in 7.9% Throughout the study period, the commonest manifestation was oral ulcers (100%), followed by genital ulcers (96.8%), vascular lesions (57.1%), cutaneous (55.5%), ocular (47.6%), joint (36.5%), neurological (34.9%), gastrointestinal (19%) and cardiac (6.3%). BD in Egyptians shows higher male-to-female ratio and higher incidence of vascular and neurological lesions.