A B cell apotope of Ro 60 in systemic lupus erythematosus

OBJECTIVE: Previous studies have attempted to segregate anti-60-kd Ro/SSA (anti-Ro 60) responses in systemic lupus erythematosus (SLE) and primary Sj?gren's syndrome (SS) but have shown limited disease preference. The aim of the present study was to determine whether the presence of autoantibodies against an Ro 60 apotope (an epitope expressed on apoptotic cells) distinguishes anti-Ro 60 responses in SLE and primary SS. METHODS: Multiparameter flow cytometry was used to select early apoptotic cells and measure the simultaneous binding of annexin V, propidium iodide, and anti-Ro 60-positive IgG from SLE patients (n=21) and patients with primary SS (n=19). The specificity of the Ro 60 apotope was determined by inhibition experiments with recombinant and native Ro 60. RESULTS: Autoantibodies against the Ro 60 apotope were prevalent in SLE patients (13 of 21, 62%) and were rarely observed in patients with primary SS (1 of 19, 5%) (P=0.0002). Further, within SLE patients, autoantibodies to the Ro 60 apotope strongly distinguished patients with anti-Ro 60 alone (12 of 13, 92%) from those with both anti-Ro 60 and anti-La (1 of 8, 13%) (P=0.0005). When we considered all patients with anti-Ro 60 alone, the presence of autoantibodies to the Ro 60 apotope had both high sensitivity (92.3%) and high specificity (85.7%) for SLE compared with primary SS (P=0.0012). The presence of autoantibodies to the Ro 60 apotope may therefore be of diagnostic value in patients with isolated anti-Ro 60 responses. CONCLUSION: The preferential targeting of an Ro 60 apotope exposed on early apoptotic cells in a subset of SLE patients implies disease-specific pathways for the induction of anti-Ro 60 autoimmunity.     

Fine specificity of the Ro/SSA autoantibody response in relation to serological and clinical findings in 96 patients with self-reported cutaneous symptoms induced by the sun

Anti-Ro/SSA assays assist the clinician in distinguishing autoimmune diseases such as Sj?gren? syndrome (SS), systemic lupus erythematosus (SLE) and subacute cutaneous lupus erythematosus (SCLE). The objective of the study was to investigate the fine specificity of the autoantibodies in relation to clinical presentation as well as environmental and endogenous factors such as photosensitivity, smoking and immunoglobulin (Ig) levels in patients with Ro/SSA autoantibodies. Serum samples from 96 anti-Ro/SSA positive photosensitive patients were tested for autoantibody levels by enzyme-linked immunosorbent assay (ELISA) using purified recombinant Ro52 kd, Ro60 kd and La proteins as antigens. The highest levels of anti-Ro52 and anti-La were observed in patients with primary SS, and the lowest levels of anti-Ro52 in chronic cutaneous lupus erythematosus (CCLE). SCLE patients with systemic disease (SLE and/or SS) showed higher levels of anti-Ro52 than SCLE limited to the skin. A correlation between high serum levels of IgG and anti-Ro52 (P < 0.01) and between IgA and anti-Ro52 (P < 0.05) and anti-Ro60 (P < 0.05) was found. Polymorphic light eruption (PLE) was common in all diagnostic groups but did not correlate with autoantibody levels. Smoking was more common in lupus patients than in SS patients. Our findings thus propose different mechanisms for different clinical presentations of Ro/SSA positive patients. The testing of anti-Ro52 antibodies might serve as a prognostic tool in photosensitive cutaneous diseases.     

Can B cell epitopes of 60 kDa Ro distinguish systemic lupus erythematosus from Sj?gren's syndrome?

Antibodies binding components of the Ro/La (or SSA/SSB) ribonucleoprotein particle are found in the sera of patients with systemic lupus erythematosus (SLE) and Sj?gren's syndrome (SS) as well as mothers who give birth to babies with neonatal lupus. Anti-La occurs in a subset of sera that contain anti-Ro, and anti-La is found more commonly in sera of patients with SS than in sera from SLE patients. The fine specificity of autoantibodies binding 60 kDa has been studied extensively. Recent data have suggested that there are disease-specific epitopes which identify patients with either SLE or SS. Alternatively, other data suggest that the B cell epitopes of 60kDa Ro vary according to the presence of anti-La. The present study was undertaken to determine whether binding of putative disease-specific 60 kDa Ro epitopes is associated with the diagnosis of SLE vs SS, or instead associated with the presence of anti-La. Anti-60 kDa Ro positive sera from 24 SLE patients and 44 SS patients were studied for antibodies binding two epitopes of 60 kDa Ro. We find the epitope defined by residues 171-190 is associated with anti-60 kDa Ro without anti-La, regardless of diagnosis. Meanwhile, binding of the epitope defined by residues 215-232 is not commonly found in anti-60 kDa Ro sera, especially in those sera with both anti-60 kDa Ro and anti-La. Thus, the fine specificity of antibody binding to 60 kDa Ro varies according to the presence of anti-La, not to the diagnosis of either SLE or SS.     

Clinical and prognostic value of autoantibodies in puerto Ricans with systemic lupus erythematosus

The aim of this study was to determine the association between lupus autoantibodies and the clinical manifestations and outcome in a cohort of Puerto Ricans patients with systemic lupus erythematosus (SLE). All patients fulfilled the American College of Rheumatology classification criteria for SLE. Demographic parameters, clinical manifestations over time and damage accrual were obtained at the last study visit. Disease damage was assessed with the Systemic Lupus International Collaborating Clinics Damage Index (SDI). ANA, ANA pattern, and anti-dsDNA, anti-Smith, anti-Ro (SSA), anti-La (SSB) and anti-snRNP antibodies were measured at the time of SLE diagnosis. Chi-square test, Fisher exact test, ANOVA, logistic regression and general lineal model analyses were used to evaluate these associations. Ninety-six percent of patients were females. The cohort had a mean age of 40.2 +/- 12.0 years and mean disease duration of 9.6 +/- 7.0 years. Patients with elevated anti-dsDNA antibodies were more likely to have vasculitis, pericardial effusion, renal involvement, anaemia, leukopenia, lymphopenia and thrombocytopenia. Anti-Smith antibodies were positively associated with skin ulcerations, elevated liver enzymes, renal involvement and thrombocytopenia. Anti-Ro antibodies were related with the presence of discoid lupus, serositis, pneumonitis, elevated liver enzymes, hemolytic anaemia, leukopenia and lymphopenia. No positive associations were found for anti-snRNP or anti-La antibodies. The presence of anti-dsDNA, anti-Smith and anti-Ro antibodies was associated with higher SDI scores. In conclusion, anti-dsDNA, anti-Smith and anti-Ro antibodies are associated with several clinical manifestations and more damage accrual in Puerto Ricans with SLE. These findings provide valuable clinical and prognostic information for this ethnic population.     

Neonatal lupus manifests as isolated neutropenia and mildly abnormal liver functions

Neonatal lupus is characterized by typical clinical features and the presence of maternal autoantibodies. Mothers can have systemic lupus erythematosus (SLE) or Sj?gren's syndrome, but are commonly not affected with any clinical disease. The major clinical manifestations in the infants are cardiac, dermatological and hepatic with rare instances of hemolytic anemia, thrombocytopenia or neutropenia. We describe an infant born to a mother with anti-Ro and anti-La, who had neutropenia and mildly abnormal liver functions without other major clinical features of neonatal lupus such as cardiac or dermatological manifestations. Neutropenia improved as maternal antibody was metabolized. Antibodies from both the infant and mother bound intact neutrophils, and this binding was inhibited by 60 kDa Ro. These data imply neutropenia may be an isolated manifestation of neonatal lupus. We studied the anti-Ro antibodies of 2 other mothers who gave birth to infants with complete congenital heart block and neutropenia. Their sera also bound neutrophils. Because healthy infants do not commonly undergo complete blood counts, the incidence of neutropenia among infants of anti-Ro-positive mothers may be much higher than previously recognized. Furthermore, although other factors may contribute, these data suggest that anti-60 kDa Ro is directly involved in the pathogenesis of neutropenia.     

A model for disease heterogeneity in systemic lupus erythematosus. Relationships between histocompatibility antigens, autoantibodies, and lymphopenia or renal disease

We composed a model from autoimmune serologic findings, HLA antigens, and clinical findings that explains, at least partially, the clinical heterogeneity of 40 patients with systemic lupus erythematosus (SLE). In these patients, anti-RO (SS-A) was related to the HLA-DQ1/DQ2 heterozygotes, anti-La (SS-B) was related to HLA-B8 and HLA-DR3, and anti-nuclear RNP (Sm) was related to HLA-DR4. Lymphopenia was associated with anti-Ro (SS-A) and, secondarily, with anti-single-stranded DNA. Renal disease in these SLE patients was inversely associated with anti-La (SS-B) and was positively associated with anti-double-stranded DNA. There were no associations between the HLA antigens and these clinical manifestations. The results support a model of disease expression in which individuals are nonspecifically potentiated for SLE. Their HLA antigen composition influences the production of particular autoantibodies that are related in complex ways to the different particular clinical findings of SLE manifested in individual patients.     

PREVALENCE AND CLINICAL SIGNIFICANCE OF ANTIBODIES TO RIBONUCLEOPROTEINS IN SYSTEMIC LUPUS ERYTHEMATOSUS IN MALAYSIA

One hundred and seventy patients with systemic lupus erytbematosus(SLE) were studied for the prevalence of antibodies to the smallRNA-associated proteins Ro/SSA, La/SSB, Sm, UIRNP and Sm. Therelationship of these autoantibodies to different races, sexesand clinical manifestations of SLE was evaluated. Passive immunodiffusionwas employed using human spleen extract as antigen source forRo and rabbit thymus extract for La, Sm and UIRNP. We foundthe prevalence of antibodies to be as follows: anti-Ro/SSA,36%; anti-La/SSB, 8%; anti-Sm, 15%; anti-UIRNP, 21%. Exceptfor a low prevalence of anti-La, the prevalence of these antibodieswas similar to that in Western studies. The prevalence of anti-Ro/SSAis similar to that reported in the Western studies, but lowerthan that reported in other Oriental patients from Singaporeand Hong Kong. Linkages of anti-Ro with anti-La antibodies wereusual; however, although anti-Sm antibodies were usually associatedwith anti-UIRNP, they were more frequently associated with anti-Roantibodies. The Malay patients had a high prevalence of anti-UIRNPcompared to other races. No gender difference was detected.Anti-Sm antibody was associated with scrositis and anti-UIRNPantibodies with Raynaud's phenomenon. No association was foundbetween the presence of skin, renal or cerebral manifestationsand any specific antibodies or combination of antibodies. KEY WORDS: Systemic lupus erythematosus, Racial comparison, Ro/SSA, La/SSB, Sm, UIRNP     

Anti-La (SS-B): a diagnostic criterion for Sj?gren's syndrome?

We examined the diagnostic sensitivity and specificity of antibodies to Ro (SS-A) and La (SS-B) in Sj?gren's syndrome (SS) by counterimmunoelectrophoresis and immunodiffusion. Anti-Ro was found in 56% and anti-La in 42% of patients with SS and in 38% and 6% respectively in SLE. Anti-La was rare (less than 1%) in other connective tissue diseases. As a more stringent test of diagnostic specificity, 88 patients whose sera contained anti-La and/or anti-Ro were carefully examined for evidence of Sj?gren's syndrome. Of 35 patients whose sera contained anti-La, 29 (83%) fulfilled criteria for SS, and four out of 6 of the remainder showed some evidence of early disease. Of 53 patients with anti-Ro (without anti-La), only 42% had Sj?gren's syndrome, 45% had SLE and 13% other connective tissue diseases. These data confirm that anti-La, but not anti-Ro, has a high diagnostic specificity for Sj?gren's syndrome and merits inclusion as separate diagnostic criterion for the disease.     

Anti-Ro antibody and cutaneous vasculitis in systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is a complex systemic autoimmune disease with various clinical and serological manifestations. Previous studies have shown the association of SLE and anti-Ro antibody with a series of clinical manifestations. We investigated this association in Brazilian patients with SLE. Five hundred and nine consecutive patients who fulfilled the revised American College of Rheumatology criteria for the SLE were enrolled in the study from June to December 2007. All patients were from our Service of Rheumatology, School of Medicine, University of São Paulo, Brazil. Frequencies of a series of laboratorial and clinical manifestations were calculated. Anti-Ro antibody was associated to anti-La antibody, female, and cutaneous vasculitis. In multivariate analysis, patients with anti-Ro antibody has 1.63 (95% CI 1.07–2.50) more risk to develop cutaneous vasculitis than patients without this antibody. Our data have demonstrated that anti-Ro antibody is an independent useful serologic marker for cutaneous vasculitis.     

Serial analysis of Ro/SSA and La/SSB antibody levels and correlation with clinical disease activity in patients with systemic lupus erythematosus

OBJECTIVE: To investigate the temporal correlation between anti-Ro/SSA and anti-La/SSB antibody levels and compare them with variation in clinical disease activity in patients with systemic lupus erythematosus (SLE). METHODS: Sequential serum samples collected over 18-44 months from 18 anti-Ro/SSA positive patients with systemic lupus erythematosus were analysed by ELISA with recombinant Ro60, Ro52 and La antigens. Disease activity was assessed by the BILAG index. RESULTS: Limited antibody level variation over time was found in most patients, but a subset displayed more changes and a co-variation between the levels of separate specificities was found in 40% of patients. In two patients antibody levels fluctuated with the global score. Antibodies also correlated with separate organ/systems involvement in individual patients. CONCLUSION: The Ro60, Ro52 and La antibody profile is fixed at an early stage of disease and in most patients hardly changes. Patients with fluctuating levels tend to have a co-ordinated expression of these autoantibodies.     

Diagnostic and prognostic significance of measuring antibodies to alpha-fodrin compared to anti-Ro-52, anti-Ro-60, and anti-La in primary Sjögren's syndrome

OBJECTIVE: To compare sensitivity and specificity of autoantibodies to alpha-fodrin with conventional anti-Ro and anti-La antibodies in patients with primary Sj?gren's syndrome (pSS). Data on internal organ manifestations were correlated with presence of autoantibodies. METHODS: We collected clinical and laboratory data from 321 patients with pSS (Copenhagen criteria), of which 205 fulfilled the new American-European 2002 consensus criteria. Sera were tested for autoantibodies against alpha-fodrin and recombinant Ro-52, Ro-60, and La proteins. RESULTS: Antibodies to alpha-fodrin were not diagnostically superior to conventional anti-Ro/La testing. IgG anti-La had the highest specificity (97%). A highly significant association was found between presence of anti-La and internal organ manifestations (OR 6, 95% CI 2.99-12.03) or hematological abnormalities. The pattern of autoantibodies was relatively independent of disease duration, indicating that these antibodies appeared early in pSS, probably even years before the first symptoms were manifest. CONCLUSION: We could not confirm that antibodies to alpha-fodrin had higher specificity or sensitivity than anti-Ro/La. Anti-La antibodies were strongly correlated to organ involvement and cytopenias, and thus could serve as a prognostic marker in pSS.     

Ro/SSA and La/SSB specific IgA autoantibodies in serum of patients with Sjögren's syndrome and systemic lupus erythematosus

OBJECTIVE: To investigate the occurrence of IgA autoantibodies to Ro 52 kDa, Ro 60 kDa and La antigen in serum of patients with primary Sj?gren's syndrome (pSS) and systemic lupus erythematosus (SLE). METHODS: Recombinant Ro 52 kDa, Ro 60 kDa and La antigens were used to analyse autoantibodies in serum from 25 patients with pSS, 30 patients with SLE and 20 controls using a semiquantitative immunoblotting approach. RESULTS: Among the patients with pSS, 21 (84%) had detectable IgA autoantibodies to Ro 52 kDa, 13 (52%) to Ro 60 kDa and 20 (80%) to La antigen. The corresponding results for the patients with SLE were 22 (73%), 14 (47%) and 20 (67%), respectively. No IgA autoantibodies against the three antigens were detected in 20 normal controls. A comparison of several clinical features with the titres of IgA antibodies to Ro 52 kDa, Ro 60 kDa and La, revealed a significant relation between IgA anti-Ro 52 and IgA anti-La to sicca (p< 0.05). Semiquantitative data suggest that IgG is the dominating antibody to the three antigens followed by IgM > IgA in both SLE and pSS patients. Specificity studies of IgA autoantibodies with different subfragments of Ro 52 kDa and Ro 60 kDa antigens showed that IgA antibodies did not differ from IgG and IgM in their recognition pattern. CONCLUSION: These results suggest that besides IgM and IgG, IgA autoantibodies are also detected at high frequency in patients with pSS and SLE. Further studies are necessary to evaluate the contribution of these IgA autoantibodies to inflammation as well as their diagnostic value.     

Immunological and clinical differences between juvenile and adult onset of systemic lupus erythematosus.

INTRODUCTION: Systemic lupus erythematosus (SLE) in children usually follows a more severe course than in adults, but sometimes in the previous studies reported there are many confounding factors. OBJECTIVE: To analyse the immunological and clinical characteristics of SLE juvenile onset and SLE adult onset. METHODS: We studied 179 patients with SLE, 49 patients were aged 6-18 yrs at onset of disease. Anti-dsDNA antibodies were detected by radioimmunoassay and antibodies to extractable nuclear antigens (ENA): anti-nRNP, anti-Sm, anti-Ro/SS-A and anti-La/SS-B antibodies by ELISA, counterimmuno-electrophoresis and immunoblotting. RESULTS: Juvenile-onset SLE shows a higher frequency of cutaneous vasculitis (44.8% vs 27.6%; P < 0.05), seizures (18.3% vs 7.6%; P < 0.05) nephropathy (67.3% vs 48.4%; P < 0.025), and discoid lupus erythematosus (26.5% vs 13.8%; P < 0.05). The incidence of articular manifestations is lower than in adults (85.7% vs 96.1%; P < 0.025). No significant differences were found between the two groups in relation with the prevalence of antinuclear antibodies. CONCLUSIONS: Juvenile-onset SLE has more frequent neurological and renal manifestations than adult-onset SLE, but immunological markers are similar in both groups. These features suggest the most severe clinical manifestations in the juvenile-onset SLE group are not related with the presence of studied antibodies by different methods.     

ANA negative systemic lupus erythematosus sera revisited serologically

OBJECTIVE: To better define the serology of a panel of sera from patients with a clinical diagnosis of systemic lupus erythematosus (SLE) or subacute cutaneous lupus erythematosus (SCLE) with a negative antinuclear antibody (ANA) test on mouse liver. METHODS: Sensitive ELISA methods for anti-Ro/SSA, anti-La/SSB, and anti-U1RNP were applied to a panel of 76 sera with either SLE or SCLE and a negative ANA test on mouse liver. RESULTS: These sera had previously been shown to have a high prevalence of anti-Ro/SSA (68%) and anti-La/SSB (27%) precipitins respectively. None had precipitins to U1RNP or Sm. ELISA methodology revealed that all of the sera 76/76 (100%) had elevated levels (> mean +/- 2 SD of a panel of 21 normal sera) of anti-Ro/SSA, 36/76 (46%) had elevated levels of anti-La/SSB, and 27 of 76 (35%) had elevated levels of anti-U1RNP. CONCLUSION: The subset of patients with SLE and SCLE with a negative ANA test on mouse liver almost uniformly have antibodies to the Ro/SSA antigen by a sensitive ELISA. This adds evidence to the idea that this is a more homogeneous disease subset within the spectrum of SLE.     

Anti-CCP in systemic lupus erythematosus patients: a cross sectional study in Brazilian patients

Recently, it has been found that some lupus patients may have anti-cyclic citrullinated peptide antibodies (anti-CCP), although the clinical significance of such finding is not well established. Systemic lupus erythematosus (SLE) patients may have joint complaints that are very similar to those observed in rheumatoid arthritis (RA). In early stages of disease, this form of arthritis can be difficult to differentiate from RA, so it is not rare that some SLE patients are initially misdiagnosed to have this disease. This study aims to investigate the prevalence of anti-CCP in SLE patients from Southern Brazil and its association with clinical and serological profiles. One hundred nine SLE patients were studied for anti-CCP and compared with data of 156 RA patients and 100 healthy volunteers. Comparison of clinical and autoantibody profile of anti-CCP-positive and anti-CCP-negative SLE patients was done. All SLE patients positive of anti-CCP were submitted to hand and feet X-rays. Anti-CCP was positive in 15 of 109 SLE patients, and one of them had confirmed the diagnosis of rhupus. This prevalence was significantly higher than in healthy controls (p?=?0.0004) and lower than in RA patients (p?<?0.0001). No relationship could be found with clinical profile, including joint complaints. SLE patients with anti-CCP had higher prevalence of anti-Ro (p?=?0.02) and anti-La (p?=?0.004) autoantibodies, in comparison with those negative to anti-CCP. We found that 13.7 % of Brazilian patients with SLE have positive anti-CCP. Patients with anti-CCP showed higher prevalence of anti-Ro and anti-La autoantibodies than those negative for anti-CCP. Only a careful and prolonged follow-up will reveal the real clinical value of these markers in each patient individually.     

Increased prevalence of autoantibodies to ku antigen in African American versus white patients with systemic lupus erythematosus

OBJECTIVE: To investigate whether the widely varying estimates of the prevalence of anti-Ku autoantibodies are explained by racial/ethnic differences. METHODS: Consecutive African American or white patients who met the 1982 criteria for systemic lupus erythematosus (SLE) and who were evaluated over 10 years in North Carolina, Florida, and New York were tested by immunoprecipitation of K562 cell extract for anti-Ku as well as anti-nuclear RNP (nRNP)/Sm, anti-Ro/SSA, and anti-La/SSB autoantibodies. RESULTS: Anti-Ku autoantibodies were detected in sera from 18 of 155 African American patients with SLE (12%) versus 0 of 126 white patients (P < 0.0001, by Fisher's exact test). Anti-nRNP (63% versus 16%; P < 0.0001) and anti-Sm (23% versus 7%; P < 0.0004) autoantibodies were also more common in the African American subset. The 2 groups had comparable frequencies of anti-Ro/SSA and anti-La/SSB autoantibodies. CONCLUSION: Anti-Ku antibodies are common in African American patients with SLE but rare in whites, probably explaining the different estimates of their prevalence. In African Americans, the frequency is comparable with that of anti-La/SSB. Along with anti-Ku, anti-nRNP and anti-Sm autoantibodies are also overrepresented in African Americans, suggesting that a group of specificities is characteristically associated with SLE in African Americans.     

Statistical evaluation of different clinical and serological parameters for the diagnosis of Sj?gren's syndrome

The potential value for the diagnosis of Sj?gren's syndrome (SS) of 28 clinical and 18 serological parameters was evaluated in 38 patients with primary (1 degree) SS, 29 with rheumatoid arthritis (RA), 30 with systemic lupus erythematosus (SLE), and 22 with mixed cryoglobulinemia (MC), by means of a stepwise discriminant analysis. Twelve patients with RA, 11 with SLE, and 8 with MC had evidence of sicca syndrome and were then classified as having a secondary (2 degree) SS. When comparing the various disease groups to each other, it was always possible to select different combinations of clinical and serological variables which defined highly significant discriminant functions. In addition, some parameters appeared to have a stronger discriminant power between different disease groups. For instance, 1 degree SS was well discriminated from RA by anti-Ro antibodies (Ab) and normal C-reactive protein (CRP) levels, from SLE by normal complement levels and the positivity of rheumatoid factor, from MC by the absence of liver involvement and normal complement levels. While anti-La Ab had the highest value in differentiating patients with 1 degree from those with 2 degrees SS, anti-Ro Ab and recurrent parotid swelling seem to be typical features of patients with SS with respect to those with other connective tissue disease but without sicca syndrome.     

Alpha-fodrin autoantibodies are reliable diagnostic markers for juvenile and adult Sjogren's syndrome

Sjogren's syndrome (SS) is like other systemic autoimmune diseases, characterized by a large number of autoantigens and autoantibodies and infiltration of glandular tissue by predominantly CD4 T lymphocytes. The presence of certain autoantibodies is required for the diagnosis to be made, especially Anti-Ro/SSA and anti-La/SSB. The aim of this study is to investigate the prevalence of anti-alpha fodrin and its association with anti-Ro and anti-La in juvenile and adult SS. Thirteen cases with juvenile SS and 11 old SS patients were examined. Selection and classification of the patients was based on the revised European Community Criteria. The Juvenile SS group included 10 girls and 3 boys, their age ranged from 7 to 14 years. Adult SS group included 2 males and 9 female, their age ranged from 21 to 54 years. Blood samples were subjected to Erythrocyte sedimentation rate (ESR) mm/1 degree h, Complete blood count (CBC), Latex agglutination test for estimating rheumatoid factor (RF) and antinuclear antibodies (ANA), and assessment of Anti-alpha Fodrin IgG/IgA, anti-Ro and anti-La using ELISA. The two groups were matched for sex ratio. There was a significant difference of age (10.1 +/- 2.4 vs 35.1 +/- 9.3 yr) between both groups (P < 0.05). There was no statistically significant difference of levels of ESR, ANA and anti-Ro, anti-La and anti-alpha fodrin IgG/IgA autoantibodies concentration in the sera of SS patients in both groups (P > 0.05) although their levels were elevated. The percentage of detection of anti-Ro, anti- La and anti-alpha fodrin IgG and IgA antibodies in the sera of Juvenile SS was 61.5%, 53.8%, 53.8% and 61.5% respectively, while in adult SS was 63.6%, 45.5%, 45.5% and 81.8%, respectively. Anti alpha fodrin IgA and IgG were positively detected in SS patients who had negative anti-Ro and/or anti-La. The anti-alpha fodrin IgG and IgA antibodies did not significantly correlated with antibodies against Ro and La, ESR and ANA (r < 0.25, P > 0.05). The detection of anti-alpha fodrin antibodies may prove to be a useful sensitive marker for SS. Routine screening of alpha fodrin antibodies is a valuable tool for the diagnosis of SS.     

Sj?gren's syndrome. Influence of multiple HLA-D region alloantigens on clinical and serologic expression

The relationships of HLA-DR and the newer DS (second D locus) B cell alloantigens (MB and MT) to the clinical and serologic expression of primary and secondary forms of Sj?gren's syndrome (SS) were examined in 102 patients (86 whites and 16 blacks). Although HLA-DR3 was significantly increased in whites (25 of 50, 50%) and blacks (4 of 5, 80%) with primary SS compared with race-matched normal controls, it was not appreciably elevated in those with systemic lupus erythematosus (SLE)-SS, rheumatoid arthritis (RA)-SS, or connective tissue disease-SS. The MT2 specificity, however, was more strongly associated with primary SS (86% of whites and 100% of blacks) and also with SLE-SS and RA-SS compared with race-matched normal controls. Furthermore, MT2 was significantly increased in SLE-SS and RA-SS when compared with non-sicca SLE and RA controls. Although primary and secondary SS were most strongly associated with this DS specificity (MT2), the anti-Ro (SS-A) and anti-La (SS-B) antibody responses were more closely allied to DR antigens. HLA-DR3 was increased in anti-Ro positive patients, both whites and blacks, with primary SS (74%) and in total anti-Ro positive subjects (54%) compared with their anti-Ro negative counterparts (38% and 31%, respectively). Among DR3 negative patients, HLA-DR2 correlated with anti-Ro in both primary SS (83%) and in the total SS group (58%). Thus, 96% of Ro antibody positive patients with primary SS had DR3 and/or DR2, as did 80% of anti-Ro positive subjects in all categories.(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparative analysis of autoantibodies against a-fodrin in serum, tear fluid, and saliva from patients with Sjögren's syndrome

OBJECTIVE: To evaluate levels of IgA and IgG antibodies against a-fodrin in serum, tear fluid, and saliva and compare them with anti-Ro and anti-La antibody levels in the same samples of patients with Sj?gren's syndrome (SS). METHODS: Samples from 25 patients with SS (17 primary and 8 secondary), 8 patients with systemic lupus erythematosus (SLE), and 7 patients with rheumatoid arthritis (RA) as well as 20 healthy blood donor controls were collected. Antibodies were measured using ELISA. RESULTS: Although 40% of patients with primary SS had IgG anti-a-fodrin in their sera, it was also found in 36% and 32% of samples of their tear fluid and saliva, respectively. IgA a-fodrin antibodies were detected in 32% of SS sera, 20% of tear fluid samples, and 32% of saliva samples. Although the level of IgG anti-a-fodrin was significantly greater in serum, tear fluid, and saliva of SS patients compared to controls (p < 0.001), a significant difference was observed only in serum and saliva. While anti-Ro was detected in 48%, 56%, and 24% of serum, tear fluid, and saliva samples, respectively, anti-La was found in 40%, 44%, and 28%. Significant association was observed between serum IgG antibodies against a-fodrin and dry eye symptom score and rose bengal staining score. A negative association was also noted between tear IgA antibodies against a-fodrin and Schirmer I test. CONCLUSION: Correlation of IgG and IgA antibodies against a-fodrin with the severity of eye involvement suggests that these autoantibodies may be considered activation markers of SS.