HLA-DR antigens in systemic lupus erythematosus: association with specificity of autoantibody responses to nuclear antigens.

HLA-DR antigens and autoantibodies to the nuclear or cytoplasmic antigens Ro/SSA, La/SSB, Sm, and RNP were determined in North American and Austrian patients with systemic lupus erythematosus (SLE). Analysis of the association of antibodies to these ribonucleic acid (RNA)-protein antigens with HLA-DR antigens showed that HLA-DR3 was related to the presence of anti-Ro/SSA or anti-La/SSB, or both. In contrast, anti-Sm or anti-RNP, or both were associated with HLA-DR4. HLA-DR5 was associated with absence of these autoantibodies. The data extend evidence for the complexity and heterogeneity of SLE. Moreover, they indicate that, in SLE, genes linked to those coding for HLA-DR antigens, are related to the specificity of autoantibody responses rather than to the primary immunological abnormalities of this disorder.     

HLA antigens in systemic lupus erythematosus.

Forty-five patients suffering from systemic lupus erythematosus were studied in respect of their serologically defined HLA antigens. HLA-B8 antigen was found in 37-8% of patients as compared to 22% of controls. Individuals carrying the HLA-B8 antigen have a 2-15 times greater risk of developing systemic lupus erythematosus than those not carrying this antigen.     

HLA antigens associated with systemic lupus erythematosus in Japan

We studied whether or not HLA-A,B,C and DR antigens were associated with clinical and immunological findings in 116 patients with systemic lupus erythematosus (SLE) in Japan. SLE patients tended to be associated with HLA-DR2, compared with 75 healthy individuals. Among the SLE patients, there was an association between HLA antigens and the presence or absence of certain clinical or immunological features. Different HLA antigens might have a predictive value for SLE and/or the same clinical and immunological abnormalities between Caucasian and Japanese SLE patients.     

Immunoblotting profiles in 55 systemic lupus erythematosus sera lacking precipitating antibodies to extractable nuclear antigens.

Serum samples from 55 patients with systemic lupus erythematosus (SLE) were selected for the absence of anti-extractable nuclear antigen antibodies after routine immunodiffusion tests. These sera were immunoblotted for anti-Sm and anti-RNP antibodies on a HeLa cell nuclear extract. Ten (18%) were negative and 45 (82%) produced complex patterns: 10 (18%) suggestive of anti-Sm, three (5%) anti-RNP, and 32 (58%) a combination of anti-Sm and anti-RNP antibodies. These data were very similar to those obtained from sera from a control group of 28 SLE sera selected for positivity of anti-Sm and anti-RNP precipitins with the immunodiffusion test. IgM isotype antibodies to the D peptide were significantly more prevalent than IgG isotype antibodies, whereas antibodies to the 68 kD polypeptide were of both IgM and IgG isotypes. Sera with an anti-Sm/RNP immunoblotting pattern stemmed from a group of patients with SLE with a higher titre of anti-dsDNA antibodies. Among clinical symptoms, the incidence of haemolytic anaemia was higher in the group of patients with the anti-Sm immunoblotting profile. Patients with an anti-RNP immunoblotting profile showed a higher incidence of cutaneous symptoms. It is concluded that immunoblotting for anti-Sm or anti-RNP antibody determination is a very sensitive diagnostic tool in patients with SLE.     

Lymphocyte response to virus antigens in systemic lupus erythematosus

The cell-mediated immune response of lymphocytes to rubella, measles, parainfluenza types 1, 2, and 3, varicella-zoster, and herpes virus type 1 virus antigens was evaluated in 15 SLE patients and 15 matched controls by incorporating ³H-thymidine in whole blood cultures as a measure of blastic transformation. SLE patients were less responsive than normal individuals to six of eight virus antigens tested. Culture of washed SLE cells in AB plasma did not reverse the hyporesponsiveness. The results indicated that a functional impairment of the circulating lymphocytes appeared to be responsible for the in vitro hyporesponsiveness of SLE patients to virus antigens.     

Survivorship in systemic lupus erythematosus. effect of antibody to extractable nuclear antigen

The course of 81 patients with systemic lupus erythematosus (SLE) who had sera tested for antibody to extractable nuclear antigen (ENA) was studied to determine the effect of the presence of antiENA antibody on survivorship. There were no differences in percent survival between the patients with and without antibody to ENA or those with and without antibody to the ribonucleoprotein (RNP) component of ENA. We conclude that there is no prognostic advantage to the presence of either antiENA or antiRNP antibody in patients with SLE.     

HLA-DR antigens and anticardiolipin antibodies in northern Italian systemic lupus erythematosus patients

Eighty systemic lupus erythematosus (SLE) patients attending 3 clinical centers were evaluated immunologically and immunogenetically. No HLA class II antigens were found to be significantly associated with SLE in these patients. A highly significant (P = 6.17 x 10(-7) association was observed between anticardiolipin antibodies and DR7. A lesser association (P less than 0.025) was also observed between DR2 and/or DR3 and anti-Ro (SS-A) antibodies. No relationship was found between any DR antigen and anti-Sm/RNP, anti-double-stranded DNA, or anti-La (SS-B) antibodies.     

HLA alloantigens in Greek patients with systemic lupus erythematosus

The frequency of the HLA-A, -B and -DR alloantigens was studied in 74 unselected, consecutive, unrelated Greek patients with systemic lupus erythematosus (SLE) and the results were compared with those of healthy controls (380 for the class I antigens and 154 for the class II antigens). No statistically significant differences were noted between patients and controls regarding the prevalence of any class II antigen. Furthermore, no such differences were observed between our 36 anti-Ro (SSA) positive and the rest of our SLE patients. However, the coexistence of anti-Ro (SSA) and anti-La (SSB) antibodies (9 patients) correlated significantly with HLA-B8, whereas the haplotype HLA-B8DR3 was more common in the anti-Ro (SSA) positive patients than in the rest-although the difference did not reach statistical significance. The combination of high anti-ds-DNA and low C4 serum levels correlated with absence of HLA-DR5. Our findings, while in agreement with those of certain previous studies, are somewhat different from those of others. The differences may at least partly be related to variations in the control populations employed. On the other hand some of the differences, in accordance with other peculiarities of Greeks with connective tissue disease, emphasize the role of racial and/or ethnic background in the HLA-association of various autoimmune diseases and the fact that the detectable HLA alloantigens in certain diseases modify disease and autoantibody expression rather than being responsible for the autoimmune process itself.     

Serologic response to Epstein-Barr virus antigens in patients with systemic lupus erythematosus: a controlled study

Previous studies showed a link between systemic lupus erythematosus (SLE) and Epstein-Barr virus (EBV) infection. We sought to determine the features of serologic response to EBV in SLE patients and whether this response differs from those of systemic sclerosis (SSc) and primary antiphospholipid syndrome (PAPS) patients as well as healthy individuals. Sera from 198 consecutive SLE patients have been tested to detect IgG antibodies to EA/D, EBNA-1, VCA P18 and for comparison, cytomegalovirus (CMV) using commercially available ELISA kits (Trinity Biotech, USA). Forty-six SSc patients and 38 PAPS patients were enrolled as diseased control groups and sixty-five individuals as healthy controls. Significantly more SLE (54%, P?=?0.001, OR 5.77, 95% CI 2.8?C11.6), SSc (41.3%, P?=?0.005, OR 3.4, 95% CI 1.4?C8.2) and PAPS sera (36.8%, P?=?0.023, OR 2.86, 95% CI 1.14?C7.22) reacted against EA/D than healthy controls (16.9%). The mean age of anti-EA/D-positive SLE patients was significantly higher, and their disease duration was longer compared to anti-EA/D-negative SLE patients (41 ± 14 vs. 33.8 ± 10.8?years, P?<?0.001 and 100 ± 73 vs. 71 ± 62?months, P?=?0.003). In SLE patients, EA/D reactivity was associated with Raynaud??s phenomenon and the presence of any anti-ENA antibodies. Although it did not reach a statistical significance, anti-EBNA-1 reactivity was slightly lower in patients with SLE. The frequency of anti-CMV Ig G positivity was found significantly higher in SLE patients (100%) when compared to patients with SSc (95.7%), PAPS (94.7%) and healthy controls (95.4%) (P?=?0.035, P?=?0.025 and P?=?0.015 respectively). Our results support the proposed link between EBV and SLE. The finding that SSc and PAPS patients also have increased frequency of anti-EA/D response has revealed that this immune interaction may not be unique to patients with SLE, and there may be a common mechanism involving EBV in these autoimmune diseases.     

Elevated serum level of soluble HLA class I antigens in patients with systemic lupus erythematosus

Objective. To examine the clinical significance of serum soluble HLA class I antigens (sHLA class I) in patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Methods. Serum levels of sHLA class I were measured by enzyme-linked immunosorbent assay, using a monoclonal antibody against monomorphic determinant of HLA class I (W6/32) and an enzyme-labeled polyclonal antibody to human β₂-microglobulin. Results. The serum sHLA class I concentration was 1.85 ± 1.15 μg/ml (mean ± SD) in 27 patients with SLE (P < 0.0001 versus normal controls, P = 0.0001 versus RA), 0.61 ± 0.34 μg/ml in 16 patients with RA (P = 0.02 versus normal controls), and 0.41 ± 0.20 μg/ml in normal controls. The HLA class I levels were significantly correlated with the SLE Disease Activity Index (r = 0.62, P = 0.0004) and with a reduction of CH50 levels (r = −0.60, P = 0.0007). A longitudinal analysis of patients with SLE indicated that serum sHLA class I levels fluctuated in conjunction with other disease activity markers. Conclusion. Serum sHLA class I may be useful as a disease activity marker of SLE. The mechanism of secretion and the physiologic role of sHLA class I require further study.     

Development of the anti-Ro autoantibody response in a patient with systemic lupus erythematosus

Objective. To characterize the initial events in anti-Ro production by a patient with systemic lupus erythematosus, in whom this autoantibody is developing. Methods. The immune response to the Ro ribonucleoprotein and other autoantigens were studied by enzyme-linked immunosorbent assay for IgG and IgM, by isoelectric focusing, and by inhibition studies to determine apparent avidity. Results. The patient's sera showed an oligoclonal response to Ro that increased in complexity and affinity with time. IgM anti-Ro appeared shortly before IgG anti-Ro, and disappeared as IgG anti-Ro increased in titer and affinity. IgG antiribosomal P autoantibodies also appeared during the patient's course, but in contrast to anti-Ro, were not preceded by IgM antiribosomal P. Conclusion. These data are consistent with the Ro autoantigen being presented and processed in a manner similar to heterologous antigen, and with differences in the mechanisms that lead to the production of IgG anti-Ro autoantibodies as opposed to antiribosomal P autoantibodies.     

Differences in HLA antigens between patients with mixed connective tissue disease and systemic lupus erythematosus.

Patients with mixed connective tissue disease (MCTD, n = 32) or systemic lupus erythematosus (SLE, n = 60) were typed for HLA-A, B, C, Dw, and DR antigens. All patients with SLE fulfilled at least four criteria of SLE and the patients with MCTD met the criteria proposed by Alarcon-Segovia (1989). The presence of antibodies to Sm was not considered as an exclusion for MCTD. In the patients with SLE, Dw3, DR3, and the associated B8 and A1 antigens were increased, whereas in the patients with MCTD an increased frequency of Dw4 was found (45 v 18% in controls v 14% in SLE). Of the subtypes of DR4, Dw4 was present in all but one of the DR4 positive patients. The frequency of DR4 in patients with MCTD (52%) differed significantly from that of controls (28%). The strong association of MCTD to one DR4 subtype was further seen in the significantly increased frequency of the B15, DR4 combination. Thus the genetic background seems to be different in patients with MCTD from that in patients with SLE. This could partly explain the clinical differences between these diseases.     

HLA-DP genotyping in patients with systemic lupus erythematosus: correlations with autoantibody subsets.

In order to ascertain whether the HLA-DP locus plays a role in the genetic predisposition for systemic lupus erythematosus (SLE), 42 patients with SLE were typed for 17 different DPBeta haplotypes by locus specific amplification followed by allele specific oligonucleotide hybridization. Sera from the same patients were assayed for the presence of autoantibodies to Sm, RNP, Ro, La and of anticardiolipin antibodies (aCL). DPB1*0301 and DPB1*1401 were increased in patients compared with 107 healthy controls, mainly in those anti-Sm/RNP positive and aCL positive. Remarkably, DPB1*1401 and DPB1*0301 have a nearly identical nucleotide sequence, suggesting that an epitope shared by their membrane products is of major importance for the DP related susceptibility to SLE.     

Disease expression and class II HLA antigens in systemic lupus erythematosus.

The aim of this investigation was to examine the relationship between Class II HLA antigens and disease expression in systemic lupus erythematosus (SLE). HLA-DR and DQ antigen frequency was studied serologically in 217 SLE patients followed prospectively and compared to 320 healthy controls. The relationship between HLA antigens and the presence of disease manifestations, as well as death was investigated in 117 SLE patients enrolled within the first year of their disease. A univariate analysis confirmed the association between HLA-DR3 and SLE. HLA antigen DR1, DR6, DR7, DQw1 and DQw3 were decreased in patient group compared to the controls. A logistic regression model showed a significantly negative association with HLA-DR1, DR6 and DR7, and a positive association with HLA-DR3. The reduced frequency of HLA-DQw1 and DQw3 was maintained using a logistic procedure. Cox Proportional Hazards models revealed no association between HLA-Class II antigens and death. Logistic regression models revealed no associations between central nervous system (CNS) disease nor musculoskeletal manifestations with any of the DR antigens. There was a trend towards a lower frequency of HLA-DR6 in patients with renal involvement and lower prevalence of HLA-DR1 and HLA-DR7 in patients with vasculitis.     

HLA class II antigens associated with systemic lupus erythematosus in black South Africans.

OBJECTIVE--To assess the associations of HLA class II antigens with systemic lupus erythematosus (SLE) in black South Africans. METHODS--HLA-DRB1 genotype frequencies assigned by polymerase chain reaction (PCR) amplification and sequence specific oligonucleotide probes were compared between 49 black SLE patients from Baragwanath Hospital and 87 ethnically matched controls. HLA-DQA1 and -DQB1 genotypes were also assigned in 45 of the SLE patients and 74 controls by PCR using sequence specific primers. RESULTS--HLA-DRB1*02 was increased in the patients compared with controls (odds ratio = 3.67; 95% confidence interval = 1.49 to 9.02; p < 0.005). HLA-DQB1*0201 was not associated with development of the disease itself, but was associated with the presence of Ro antibodies (p = 0.01). HLA-DRB1*03 was less strongly linked to DQB1*02 in this population than in white populations and was not associated with SLE. CONCLUSIONS--In black South Africans there is evidence for a locus on DR2 haplotypes contributing to SLE. Another gene, possibly HLA-DQB1*02, not linked to DR2 is involved in the subset of patients exhibiting Ro antibodies.     

Studies of Filipino patients with systemic lupus erythematosus: autoantibody profile of first-degree relatives

This study surveyed the frequency of autoantibodies among un-affected first-degree relatives (FDRs) of Filipino systemic lupus erythematosus (SLE) patients compared with healthy un-related Filipino controls. The sensitivity, specificity and predictive value of the autoantibodies for SLE diagnosis were also assessed in this Filipino cohort. Filipino patients included in the University of Santo Tomas (UST) Lupus Database and un-affected FDRs were recruited. Healthy controls included those with no known personal or family history of autoimmune disease. The following autoantibodies were tested in all subjects: anti-nuclear antibody (ANA), anti-dsDNA, anti-Ro/SSA, anti-chromatin, anti-thyroid microsome, and anti-cardiolipin antibodies. Participants included 232 SLE patients, 546 FDRs, and 221 healthy controls. Median age of patients was 27 (range 8-66) years with median disease duration of 27.5 (range 1-292) months. Median age of FDRs was 42.0 (range 5-87) years. Compared with healthy controls, there were significantly more FDRs with positive ANA at titers 1?:?40 to 1?:?160 (p?相似文献   

Anti-apolipoprotein A-I autoantibody: characterization of monoclonal autoantibodies from patients with systemic lupus erythematosus

OBJECTIVE: The autoantibody to apolipoprotein A-I (apoA-I), a major constituent of high density lipoproteins (HDL), has been detected in sera of patients with systemic lupus erythematosus (SLE). We established a series of monoclonal anti-apoA-I antibodies (MAAI) from 2 patients with SLE and report the reactivities of MAAI with oxidized HDL, anionic substances, and blood coagulation factors. METHODS: Peripheral blood B cells from patients with SLE were immortalized by Epstein-Barr virus, and B cells secreting anti-apoA-I antibodies (AAI) were fused with mouse myeloma cells. Six MAAI reactive with human apoA-I in both ELISA and immunoblotting analysis were established. The reactivities of MAAI with HDL, ssDNA and dsDNA, phospholipids such as cardiolipin (CL), and coagulation factors were examined by ELISA. RESULTS: Although all MAAI bound effectively to apoA-I after the protein had been denatured and transferred to the filter membrane (in immunoblotting analyses), they bound less effectively to apoA-I present in HDL. Both oxidation of HDL in the presence of Mn2+ and an association of apoA-I with autoxidized trilinolein strongly enhanced the binding of MAAI to apoA-I, suggesting that MAAI recognize a defined region of apoA-I, which is exposed upon interacting with oxidatively modified lipids. MAAI showed a functional heterogeneity in their cross-reactivity with self-components: some MAAI were shown to cross-react with anionic substances such as CL and ssDNA, and one MAAI was shown to bind effectively to thrombin. CONCLUSION: We identified a novel family of AAI that shows preferential binding to apoA-I in oxidatively modified HDL. These AAI are composed of antibodies with heterogeneous cross-reactivities to various self-components such as anionic phospholipids, ssDNA, and thrombin.