Search

Objectives: To investigate the clinical and immunogenetic aspects of antibody formation against Ro/SSA and La/SSB as well as their linear B cell epitopes in patients with primary Sjögren's syndrome (pSS) from different European countries., Patients and Methods: Ninety patients with pSS from six European centres were studied. Serum samples from all patients were tested in a control laboratory for anti-Ro/SSA and anti-La/SSB autoantibodies by RNA precipitation assay and autoantibodies to the previously reported B cell linear epitopes of Ro 60 kDa (p169-190aa and p211-232aa) and La/SSB (p147-154aa, p291-302aa, p301-318aa, and p349-364aa). DNA from 88 patients was used for the determination of HLA-DRB1, -DQA1, and -DQB1 genotypes. Analysis of the results was performed in the 88 patients who were genotyped and tested also for antipeptide antibodies., Results: Antibodies to B cell epitopes of Ro 60 kDa were detected at a low frequency (range 10-37%). In contrast, B cell epitopes of La/SSB were detected frequently (range 58-86%) among the anti-La/SSB positive sera. Autoantibodies to the La/SSB epitope, p349-364aa, were significantly positively associated with longer disease duration (p<0.05), recurrent or permanent parotid gland enlargement (p<0.005), and a higher proportion of non-exocrine manifestations (p<0.005), compared with patients without autoantibodies. The presence of anti-Ro/SSA and anti-La/SSB autoantibodies was significantly associated with the presence of HLA-DRB1*03 and DQB1*02 (p=0.038 and p=0.034, respectively). This association was even more prominent and extended to HLA-DQA1*0501 when patients were stratified according the presence of autoantibodies to discrete La/SSB B cell epitopes in comparison with autoantibody negative patients (p<0.01). They were found also to be highly associated with the alleles HLA-DQB1*02 and HLA-DQA1*0501 as well as the presence of a shared amino acid motif in the region 59-69aa of DQB1 first domain (p<0.01, respectively)., Conclusions: Autoantibodies against La/SSB, binding to four synthetic peptides, derived from the sequence of the La protein were identified with increased frequency in sera of patients with pSS. The formation of autoantibodies against B cell epitope analogues of La/SSB in European patients with pSS may be dependent on the presence of a permissive HLA-DQ heterodimer, most prominently represented by the HLA-DQA1*0501/DQB1*0201 heterodimer, suggesting that a model of HLA restricted presentation of La/SSB peptide determinants is crucial for the autoimmune response against La/SSB.

Objective: To study which clinical and immunological factors may be associated with low salivary and lacrimal flow in patients with primary Sjögren's syndrome (SS). Are the lacrimal and salivary flows influenced by age of the patient, age at diagnosis, disease duration, or findings in the biopsies of the minor salivary glands, or are immunological factors of importance for reduced flow rates?, Methods: In total 72 patients (mean age 57 yrs and disease duration 13.5 yrs) with primary SS diagnosed according to the European classification criteria were evaluated objectively by serological testing and by measures of exocrine gland function, such as unstimulated whole saliva collection (UWSC) and by Schirmer I test., Results: Salivary flow (UWSC) in 72 patients with primary SS correlated to the presence of antinuclear antibodies (ANA) (r = -0.32, p = 0.006) and to anti-SSA/SSB (r = -0.31, p = 0.010). No such correlation was seen for the lacrimal flow, and there was no mutual correlation between lacrimal and salivary flow. UWSC was significantly lower in patients with anti-SSA versus those without anti-SSA (1.63 ml vs 2.63 ml; p < 0.007), while such a significant difference was not observed in the presence versus absence of anti-SSB. The salivary and lacrimal flow was not significantly affected by age of the patient, and did not correlate to age at diagnosis, sex, disease duration, rheumatoid factor finding, or findings in minor salivary gland biopsies., Conclusion: Salivary flow in patients with primary SS was negatively correlated with immunological factors such as ANA and anti-SSA/SSB, in contrast to low lacrimal flow, where no such correlation was seen. There was no association of lacrimal and salivary flow with age of patient, age at diagnosis, disease duration, and findings in minor salivary gland biopsies. The results indicate that reduced salivary flow is closely associated with immunological factors, and is not associated with the age of the patient or infiltration of lymphocytes in salivary glands.

Sjögren's syndrome (SS) is a chronic autoimmune disease characterized by dryness of the eyes and mouth. Currently, the highly polymorphic major histocompatibility complex (MHC) genes are the best documented genetic risk factor for the development of autoimmune disease. We examined the MHC class II alleles DRB1, DRB3, DRB4, DRB5, DQA1 and DQB1 in a group of Norwegian pSS patients and compared with a group of healthy controls. Because a number of studies have shown that some of the MHC class II alleles are not associated with the disease as a whole, but rather to the development of autoantibodies, anti-Ro52 autoantibodies in serum were measured and compared to MHC class II allele status. A clear association with pSS was detected for the DRB1*0301 and DRB3*0101 alleles, but these alleles were more closely associated with the presence of anti-Ro52 autoantibodies than with pSS itself. Moreover, the DQA1*0501 and DQB1*0201 alleles were only associated with the presence of anti-Ro52 autoantibodies. This study shows that the production of anti-Ro52 autoantibodies in pSS is associated with the DRB1*0301, DRB3*0101, DQA1*0501 and DQB1*0201 alleles which are in strong linkage disequilibrium.

Objective: To investigate and identify the presence of cells producing anti-Ro/SSA and anti-La/SSB autoantibodies in salivary glands from patients with Sjögren's syndrome (SS)., Methods: Submucosal salivary gland biopsy samples from 10 SS patients (8 with and 2 without circulating Ro and La autoantibodies) and 14 control subjects were evaluated. Frozen tissue sections were immunostained by an avidin-biotin complex technique, using biotinylated recombinant Ro and La proteins as detection reagents. Autoantibody levels in SS patient sera were analyzed by enzyme-linked immunosorbent assay., Results: Cells producing autoantibodies to the Ro 52-kd, Ro 60-kd, and La proteins were recorded in 8, 6, and 7 of the 10 SS patient biopsy samples, respectively. Samples from the 2 SS patients without circulating Ro and La autoantibodies were negative for these autoantibody-producing cells, as were all control biopsy samples. A strong positive correlation between the presence of autoantibodies in sera and the presence of autoantibody-producing cells in glandular biopsy tissues was evident. The number of autoantibody-producing cells and the serum autoantibody levels were also correlated (r(s)=0.94, P < 0.0001)., Conclusion: Using a novel technique, we have demonstrated the presence of Ro and La autoantibody-producing cells in salivary gland biopsy tissues from patients with SS. These findings indicate that anti-Ro/ SSA and anti-La/SSB autoantibodies are produced and are present at sites of inflammation and indicate their potential involvement in the autoimmune exocrinopathy of this disease.

During a 6-month period, 100 patients with systemic lupus erythematosus (SLE) were consecutively studied for the presence of antithyroid antibodies and thyroid disease. Overall, the prevalence of antithyroid antibodies was similar in patients with SLE (21%) and controls (16%). However, antithyroglobulin antibodies were found in 11% of patients with SLE and only 2% of controls (p = 0.009). The levels of antimicrosomal antibodies were also different (median levels: SLE = 400; controls = 100) but this difference did not reach statistical significance. We found a significant correlation between thyroid stimulating hormone (TSH) levels and the levels of both the antithyroglobulin dilutions (p less than 0.05) and the antimicrosomal dilutions (p less than 0.05). This was not seen in the controls. A higher frequency of clinical thyroid disease was seen in patients with SLE with thyroid antibodies (5/21; 3 hypothyroid, 2 hyperthyroid) than in those without these antibodies (1/79; p = 0.001). Levels of antithyroid antibodies correlated with clinical or subclinical (marked by elevations of TSH) thyroid disease. Patients with SLE with these antibodies were significantly older (mean age 47.5 +/- 13 years) than those without antithyroid antibodies (mean age 37.5 +/- 12 years; p less than 0.001). Antithyroid antibodies define a subset of older patients with SLE with increased prevalence of both clinical and subclinical thyroid disease.