Hyporesponsiveness of lymphocytes to virus antigens in rheumatoid arthritis

The immune response of peripheral blood lymphocytes to measles, rubella, parainfluenza types 1, 2, and 3 RNA virus antigens, and to varicella-zoster and herpes virus type 1 DNA virus antigens was evaluated in 14 patients with rheumatoid arthritis (RA) and 14 matched controls by assessing ³H-thymidine incorporation. The results demonstrated hyporesponsivenss of lymphocytes from RA patients to virus antigens and phytohemag-glutinin (PHA), which did not appear to be nonspecific because of a lack of correlation between response to virus antigens and response to mitogens. The pattern of decreased responsiveness was suggestive of a relative restriction of hyporesponsiveness to RNA virus antigens.     

Hyporesponsiveness of lymphocytes to virus antigens in rheumatoid arthritis.

The immune response of peripheral blood lymphocytes to measles, rubella, parainfluenza types 1, 2, and 3 RNA virus antigens and to varicella-zoster and herpes virus type 1 DNA virus antigens was evaluated in 14 patients with rheumatoid arthritis (RA) and 14 matched controls by assessing 3H-thymidine incorporation. The results demonstrated hyporesponsivenss of lymphocytes from RA patients to virus antigens and phytohemagglutinin (PHA), which did not appear to be nonspecific because of a lack of correlation between response to virus antigens and response to mitogens. The patterns of decreased responsiveness was suggestive of a relative restriction of hyporesponsiveness to RNA virus antigens.     

Antibodies to Viral Antigens in Systemic Lupus Erythematosus

Sera from 31 patients with lupus erythematosus, 31 controls matched by age and sex and 33 patients with connective tissue disorders other than SLE were examined for specific antibodies to 15 viral antigens by hemagglutination-inhibition tests. Complement-fixation tests were also employed to measure antibodies to measles virus and rubella virus. Sera from patients with LE had significantly higher geometric mean antibody titers than matched controls to measles, rubella, parainfluenza types 2 and 3 and reovirus type 2 antigens. When antibody levels from patients with LE were compared with those from patients with other connective tissue disorders, significant differences were noted for measles, rubella, parainfluenza types 1 and 2 and mumps antigens. Removal of nonspecific antinuclear antibodies from selected SLE sera by adsorption with mouse liver nuclear antigens failed to appreciably alter specific viral antibody. The elevated antibody levels in sera from patients with SLE are consistent with the existence of a hyperreactive immunologic state in this disorder and do not necessarily carry etiologic implications.     

Natural Killer Cells in Systemic Lupus Erythematosus

A monoclonal antibody, HNK-1, that detects a differentiation antigen on human granular lymphocytes with natural killer (NK) activity was used to enumerate this subpopulation in the peripheral blood of 14 patients with systemic lupus erythematosus (SLE). Nine patients had severely decreased numbers of HNK-1⁺ cells, 3 patients had elevated levels of HNK-1⁺ cells, and 2 patients had appropriate numbers of HNK-1⁺ cells compared with the levels in 112 normal controls. All SLE patients exhibited low NK killing ability against K562 target cells compared with controls. An increased proportion of the HNK-1⁺ cells was categorized as immature granular lymphocytes in over 50% of the SLE patients because their HNK-1⁺ cells coexpressed the OKT3 antigen and contained a paucity of cytoplasmic granules. The numbers of HNK-1⁺ cells or the HNK-1⁺ OKT3⁺ subgroup did not correlate with steroid therapy. This evidence suggests that levels of HNK-1⁺ lymphoctyes are abnormal and functionally immature in most SLE patients. Longitudinal studies conducted over several months on a number of SLE patients demonstrated fluctuations in the ratio of mature and immature HNK-1⁺ cells and total HNK-1⁺ cells. Additional patients tested over longer periods of time will have to be studied to determine whether the proportion of mature NK cells (HNK-1⁺ OKT3^-) and immature NK cells (HNK-1⁺ OKT3⁺) will be useful in predicting the clinical course of disease.     

Impaired B cell proliferation by Staphylococcus aureus Cowan 1 in patients with systemic lupus erythematosus

We examined the proliferative response to Staphylococcus aureus Cowan 1 (SAC) by enriched peripheral blood B cells from patients with systemic lupus erythematosus (SLE). Responses of B cells from patients with active and inactive SLE were significantly lower than those of B cells from normal individuals. Hyporesponsiveness to SAC was not observed in healthy family members of SLE patients. This hyporesponsiveness did not correlate with prednisolone therapy and could not be attributed to serum factors; it did correlate with the presence of suppressor monocytes. However, we could not exclude the possibility of enhanced sensitivity of SLE B lymphocytes to suppressive signals delivered by the monocytes.     

An expression of anaplastic large cell lymphoma-associated antigens on HTLV-I-infected CD4+ T cells

 We investigated tumor-associated antigens induced by infection with human T-lymphotropic virus type I(HTLV-I). Anaplastic large cell lymphoma (APLL) antigens were found to be expressed on interleukin 2 (IL-2)-dependent, HTLV-I-infected CD4⁺ T-cell lines established from patients with adult T-cell leukemia and HTLV-I-associated myelopathy/tropical spastic paraparesis. However, APLL antigens were not detected on unstimulated lymphocytes, mitogen-activated T lymphocytes, or Epstein-Barr virus-infected B cells. Furthermore, APLL antigens were not found on IL-2-independent HTLV-I-transformed cells such as MT-1 or MT-2. When naive CD4⁺ T cells were infected with HTLV-I in vitro in the presence of IL-2, the APLL antigens were detected on them 4 weeks after infection. The expression level increased in a time-dependent fashion. These results indicate that HTLV-I infection induces a unique category of tumor-associated antigens on CD4⁺ T cells. Received: 16 April 1997 / Accepted: 7 October 1997     

Depressed in Vitro B—Lymphocyte Differentiation in Systemic Lupus Erythematosus

Peripheral blood lymphocytes from 20 patients with systemic lupus erythematosus (SLE) and 21 normal donors were incubated with pokeweed mitogen in order to assess in vitro terminal—differentiation of B lymphocytes into cells synthesizing intracytoplasmic immunoglobulin (Ig). Although the percentage (mean ± SEM) of B lymphocytes bearing surface Ig in the initial cell suspensions was not statistically different in SLE than in normal subjects (15 ± 2.2% versus 16 ± 1.9%, respectively), the frequency of cells containing intracytoplasmic Ig per 10³ mononuclear cells was significantly lower in mitogen—stimulated cultures derived from the patients than from the normal controls (10 ± 2.3 versus 56 ± 13.0 for IgM, P < 0.01; 21 ± 3.6 versus 63 ± 10.4 for IgG, P < 0.01; 13 ± 3.1 versus 24 ± 3.8 for IgA, P < 0.05 respectively). Coculturing active SLE lymphocytes with cells from normal subjects resulted in a significant (P < 0.05) increase in the frequency of cells containing intracytoplasmic IgG when stimulated with pokeweed mitogen. Moreover, culturing SLE lymphocytes in cell—free media derived from activated normal lymphocytes also resulted in a significant increase in the frequency of IgG—containing cells. These results suggest that B—lymphocyte differentiation in vitro is depressed in SLE and may, at least partially, be reversed by products derived from normal lymphocytes.     

Clinical relevance of the expression of P‐glycoprotein on peripheral blood lymphocytes to steroid resistance in patients with systemic lupus erythematosus

Objective

P‐glycoprotein (P‐gp) of membrane transporters leads to drug resistance by the exclusion of intracellular drugs, including corticosteroids. Some patients with highly active systemic lupus erythematosus (SLE) show poor response to corticosteroids; however, the mechanisms of steroid resistance remain unclear. The aim of this study was to elucidate the clinical relevance of P‐gp expression on lymphocytes to steroid resistance in patients with active SLE.

Methods

Flow cytometric analyses of the expression of P‐gp on peripheral blood lymphocytes from 20 normal volunteers and 80 SLE patients were performed. Steroid‐exclusion analysis of peripheral blood mononuclear cells (PBMCs) was conducted by using radioisotope‐labeled dexamethasone.

Results

P‐gp was expressed at significantly high levels on most of the peripheral blood lymphocytes from SLE patients, whereas normal lymphocytes had only marginal expression. The quantity of P‐gp on SLE lymphocytes correlated with the disease activity in each patient, as estimated by the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). Furthermore, in SLE patients whose SLEDAI scores were >12 despite taking >0.5 mg/kg/day of prednisolone, P‐gp expression on lymphocytes was markedly increased, and intracellular dexamethasone in their PBMCs was significantly decreased. However, intensive immunosuppressive treatment in these SLE patients resulted in successful control of disease activity, which occurred in parallel with a marked reduction of P‐gp on lymphocytes.

Conclusion

The overexpression of P‐gp on lymphocytes might lead to exclusion of corticosteroids from lymphocytes, resulting in steroid resistance in patients with highly active SLE. Reduction of P‐gp expression achieved by intensive immunosuppressive treatment overcame the steroid resistance. We therefore propose that measurement of P‐gp expression on lymphocytes is useful in the assessment of steroid resistance and is a good marker for indicating the need for intensive immunosuppressive treatment in patients with highly active SLE.

     

Altered metabolism of poly(adp-ribose) in the peripheral blood lymphocytes of patients with systemic lupus erythematosus

A method was developed to measure poly(ADP-ribose) metabolism in peripheral blood lymphocytes. The technique involved the isolation of lymphocytes on Ficoll gradients, followed by lysis with 5M NaCl. The synthesis and degradation of poly(ADP-ribose) in this crude lysate, measured by the incorporation of ³H-labeled NAD into acid-precipitable counts, was compared in 18 patients with systemic lupus erythematosus (SLE), 10 patients with rheumatoid arthritis, and in 10 control patients without rheumatoid arthritis. Patients with SLE showed a 70% decrease in poly(ADP-ribose) synthesis (P < 0.001); this decreased synthesis persisted even with the addition of histones or DNase. We present possible explanations of the role of poly(ADP-ribose) in SLE.     

Mapping of immunodominant CD4+T lymphocyte epitopes of Hepatitis C virus antigens and their relevance during the course of chronic infection

In acute and chronic viral disease the specific response of CD4⁺ T lymphocytes to certain viral proteins is an essential part of antiviral effector mechanisms. In hepatitis C virus infection, the contribution of the immune system and particularly of CD4⁺ T lymphocytes to the pathogenesis of disease is unknown. We serially determined the peripheral blood CD4⁺ T lymphocyte response to several recombinant hepatitis C virus proteins (core, NS3, NS4, NS5) and 17 overlapping synthetic peptides derived from the core sequence over up to 48 months in 43 patients with chronic hepatitis C; of these, 16 had been treated with interferon alfa (IFN). Twelve of 27 untreated patients, 4 of 4 sustained responders to IFN, 7 of 8 patients with a transient response, and 1 of 4 nonresponders showed a proliferative response to hepatitis C virus proteins. The hepatitis C virus core protein was the most immunogenic protein, and fine analysis with peptides indicated amino acids 23 to 42, 66 to 85, and 131 to 150 as immunodominant regions. In a subgroup of nine patients, proliferation assays were performed before or during IFN. In this subgroup, sustained responders but not those with a transient or no response to IFN showed a specific CD4⁺ immune reaction to hepatitis C viral antigens (P < .05). Infection with hepatitis C virus genotype 3a was significantly associated with a sustained response to IFN (P < .05). In general, a CD4⁺ T lymphocyte response was more common in patients with chronic hepatitis C who responded to interferon-alpha as compared with nonresponders. Thus a strong CD4⁺ reaction before and during IFN therapy may be a predictor of sustained response.     

A pilot study of the use of 2‐[18F]‐fluoro‐2‐deoxy‐D‐glucose–positron emission tomography to assess the distribution of activated lymphocytes in patients with systemic lupus erythematosus

Objective

The 2‐[¹⁸F]‐fluoro‐2‐deoxy‐D ‐glucose–positron emission tomography (FDG‐PET) technique provides information on uptake and metabolism of glucose in various tissues. Compared with resting cells, activated lymphocytes take up radioactively labeled glucose analog at a higher rate, which makes it possible to identify lymphoid organs with higher concentrations of activated lymphocytes. This study was undertaken to compare the pattern of PET images and quantitative FDG uptake in lymphoid organs of patients with active systemic lupus erythematosus (SLE) versus patients with inactive SLE and to correlate these findings with peripheral blood lymphocyte phenotypes.

Methods

Ten patients with active SLE and 9 patients with inactive SLE were studied. FDG‐PET images were obtained from the inguinal region to above the ear, starting at 60 minutes after injection of FDG. Standardized uptake values using lean body mass were determined over areas of interest.

Results

Both patients with active lupus and those with inactive lupus had increased FDG uptake in lymph nodes when compared with healthy volunteers, and there was no statistically significant difference between the 2 groups of lupus patients. Thymic uptake was demonstrated in 5 of 10 patients with active lupus compared with 0 of 9 patients with inactive disease. Three of the 5 patients with active SLE who were over 29 years of age had thymic uptake. Of the activation markers tested, only the CD3/CD71 population of cells was significantly different between the patient groups, with an increased percentage in the active disease group (P = 0.0247).

Conclusion

Increased FDG uptake in lymph nodes of both patients with active SLE and patients with inactive SLE suggests that metabolic, and probably immunologic, activity is enhanced not only in active, but also in clinically quiescent, disease. The increased thymic uptake observed only in patients with active disease suggests that the thymus plays an important role during periods of disease activity.

     

Reactivities of systemic lupus erythematosus sera with cellular and virus antigen preparations

Sera of patients with systemic lupus erythematosus (SLE) showed significantly higher complement fixation reactivities with 8 of 10 virus antigen preparations compared to sera of normal subjects, including virus workers, confirming earlier observations. However, one-third of SLE sera were also reactive with cellular antigens, prepared in a manner identical to viral antigens, but from cells not infected with virus. By contrast, only one of 49 normal sera showed reactivity with one of nine cellular antigens, at a minimal titer. Apparently heightened reactivities of SLE sera with virus antigens could be explained in many instances on the basis of reactions with cellular antigens. Serum reactivities with nonviral tissue antigens in SLE must be considered in interpretation of immunologic studies related to viruses and SLE.     

Hypertrophic Herpes Simplex Simulating Anal Neoplasia in AIDS Patients: Report of Five Cases

Abstract Five patients (4 males; mean age, 46.4 years) with painful verrucous perianal lesions caused by herpes simplex virus are described. All patients had had AIDS for a long time and were using highly active antiretroviral therapy. CD4+ counts ranged from 73 to 370/mm ³. All lesions were submitted to resection under subdural anesthesia. Histologic examinations revealed epithelial hyperplasia and dense inflammatory process, composed mainly of lymphocytes and plasma cells, extended just to the hypodermis. Immunohistochemistry was positive for herpes simplex virus Type 2 in four patients and for herpes simplex virus Type 1 in one patient, and did not detect human papillomavirus antigens. Three patients had recurrences after 3, 10, and 12 months. Resection was performed on two patients; one had a new recurrence after three months. Oral acyclovir eliminated the lesion in the third patient. The analysis of our patients suggests that herpes simplex virus, Types 1 and 2, may cause verrucous lesions simulating neoplasia in patients with AIDS using antiretroviral therapy. Presented at the Congresso Brasileiro de Coloproctologia, Campos do Jordao, Sao Paulo, Brazil, September 22 to 25, 2004.     

T cells in the myenteric plexus of achalasia patients show a skewed TCR repertoire and react to HSV-1 antigens

OBJECTIVE: The loss of myenteric neurons in the lower esophageal sphincter (LES) characterizes achalasia, an esophageal motor disorder. Because the presence of lymphocytic infiltrates suggests an immuno-mediated mechanism ongoing at the sites of disease, we investigated the T-cell receptor (TCR) repertoire and the ability to recognize human herpes virus type 1 (HSV-1) antigens of LES-infiltrating T lymphocytes in achalasia patients.
METHODS: Fifty-nine patients with idiopathic achalasia and 38 heart-beating cadaveric multiorgan donors (controls) were studied. By flow cytometry evaluation and CDR3 length spectratyping analysis, the lymphocytes of 18 patients and 15 controls were analyzed, whereas 41 patients and 23 controls were employed for functional assays.
RESULTS: Achalasia patients were characterized by a significantly higher esophagus lymphocytic infiltrate than controls (24.71%± 3.11 and 9.54%± 1.34, respectively; P < 0.05), mainly represented by CD3⁺CD8⁺ T cells. The characterization of TCR beta chain repertoire of CD3⁺ cells showed the expression of a limited number of TCR beta variable (BV) gene families (from two to five out of 26), with highly restricted spectratypes, suggesting a disease-associated oligoclonal selection of T cells. Furthermore, lymphocytes from achalasia LES specifically responded to exposure to HSV-1 antigens in vitro as showed by increased proliferation and Th-1 type cytokines release.
CONCLUSIONS: These data suggest that the oligoclonal lymphocytic infiltrate within the LES of achalasia patients may represent the trace of an immune-inflammatory reaction triggered by HSV-1 antigens and that the Th1-type cytokines released by the activated lymphocytes may contribute to establish the neuronal damage accounting for the clinical features of idiopathic achalasia.     

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 I1 antigens were found to be significantly associated with SLE in these patients. A highly significant (P = 6.17 × 1o⁻⁷) association was observed between anticardiolipin antibodies and DR7. A lesser association (P < 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, antidouble-stranded DNA, or anti—La (SS-B) antibodies.     

Systemic lupus erythematosus in adults is associated with previous Epstein‐Barr virus exposure

Objective

The possible molecular mimicry of the Epstein‐Barr virus (EBV) peptide PPPGRRP by the peptide PPPGMRPP from Sm B′/B of the human spliceosome is consistent with the possibility that EBV infection is related to the origin of systemic lupus erythematosus (SLE) in some patients. Association of EBV exposure with SLE was therefore tested for and subsequently found in children and adolescents (odds ratio [OR] 49.9, 95% confidence interval [95% CI] 9.3–1,025, P < 10⁻¹¹). These results were confirmed at the level of EBV DNA (OR > 10, 95% CI 2.53–∞, P < 0.002). Much smaller seroconversion rate differences were found against 4 other herpes viruses. Herein, we extend these studies to adults and test the hypothesis that EBV infection is associated with adult SLE.

Methods

We selected 196 antinuclear antibody–positive adult SLE patients (age ≥20 years) and 2 age‐, race‐, and sex‐matched controls per patient. SLE patients and matched controls were tested for evidence of previous infection with EBV, cytomegalovirus (CMV), herpes simplex virus types 1 and 2 (HSV‐1 and HSV‐2), or varicella‐zoster virus (VZV) by standardized enzyme‐linked immunosorbent assays.

Results

Of the 196 lupus patients tested, all but 1 had been exposed to EBV, while 22 of the 392 controls did not have antibodies consistent with previous EBV exposure (OR 9.35, 95% CI 1.45–∞, P = 0.014). No differences were observed between SLE patients and controls in the seroconversion rate against CMV, HSV‐2, or VZV.

Conclusion

These new data from adults, along with the many suggestive features of EBV infection, are consistent with the contribution of this infection to the etiology of SLE.

     

Altered lipid raft–associated proximal signaling and translocation of CD45 tyrosine phosphatase in B lymphocytes from patients with systemic lupus erythematosus

Objective

B lymphocytes from patients with systemic lupus erythematosus (SLE) exhibit defective intracellular signaling, hyperactivity, and autoantibody production. Recent evidence indicates a reduced expression of Lyn kinase, a negative regulator of B cell signaling, and reduced translocation of Lyn into membrane signaling domains in SLE. The present study was undertaken to investigate the causes of this altered regulation of Lyn by assessing the expression levels of regulatory molecules and their translocation into the signaling domains of SLE B lymphocytes.

Methods

Blood was obtained from 48 patients with SLE and 28 healthy controls for the assessment of B lymphocytes. Levels and intracellular distribution of Lyn, CD45, COOH‐terminal Src kinase (Csk), and c‐Cbl were studied by Western blotting, confocal microscopy, and flow cytometry. The kinetics of signaling molecule translocation to the B cell receptor (BCR)–antigen synapse were investigated by confocal microscopy.

Results

A profound alteration in the expression and translocation of regulatory signaling molecules in membrane domains of B cells from patients with SLE was observed. B lymphocytes from SLE patients, but not those from healthy controls, expressed a low molecular weight isoform of CD45 in lipid raft signaling microdomains. Kinetic studies revealed that translocation of Lyn, CD45, Csk, and c‐Cbl led to increased recruitment and retention of Lyn and CD45 in the BCR–antigen synapse in SLE B cells.

Conclusion

The results provide evidence of altered expression and translocation/interaction of kinases and phosphatases in membrane signaling microdomains of B cells from patients with SLE. Altered translocation of CD45 correlated with reduced expression of Lyn, indicating that Lyn is a key molecule in the regulation of BCR‐mediated signaling.

     

B cell depletion as a novel treatment for systemic lupus erythematosus: A phase I/II dose‐escalation trial of rituximab

Objective

Safer and more effective therapies are needed for the treatment of systemic lupus erythematosus (SLE). B lymphocytes have been shown to play fundamental pathogenic roles in SLE, and therefore, elimination of B cells with the use of rituximab may represent a new therapy for SLE.

Methods

A phase I/II dose‐escalation trial of rituximab added to ongoing therapy in SLE was conducted. Rituximab was administered as a single infusion of 100 mg/m² (low dose), a single infusion of 375 mg/m² (intermediate dose), or as 4 infusions (1 week apart) of 375 mg/m² (high dose). CD19+ lymphocytes were measured to determine the effectiveness of B cell depletion. The Systemic Lupus Activity Measure (SLAM) score was used as the primary outcome for clinical efficacy.

Results

Rituximab was well tolerated in this patient population, with most experiencing no significant adverse effects. Only 3 serious adverse events, which were thought to be unrelated to rituximab administration, were noted. A majority of patients (11 of 17) had profound B cell depletion (to <5 CD19+ B cells/μl). In these patients, the SLAM score was significantly improved at 2 and 3 months compared with baseline (P = 0.0016 and P = 0.0022, respectively, by paired t‐test). This improvement persisted for 12 months, despite the absence of a significant change in anti–double‐stranded DNA antibody and complement levels. Six patients developed human antichimeric antibodies (HACAs) at a level ≥100 ng/ml. These HACA titers were associated with African American ancestry, higher baseline SLAM scores, reduced B cell depletion, and lower levels of rituximab at 2 months after initial infusion.

Conclusion

Rituximab therapy appears to be safe for the treatment of SLE and holds significant therapeutic promise, at least for the majority of patients experiencing profound B cell depletion. Based on these results, controlled trials of rituximab appear to be warranted.

     

Correlation between hyporesponsiveness to Toll-like receptor ligands and liver dysfunction in patients with chronic hepatitis C virus infection

Hepatitis C virus (HCV)-associated antigens, such as the core and nonstructural antigens, activate host innate immune systems via Toll-like receptors (TLRs). We previously showed that chronic exposure to the core antigen induces hyporesponsiveness to TLR ligands in antigen-presenting cells via activation of TLR2 and that stimulation with TLR ligands results in impaired IL-6 production by peripheral blood monocytes from HCV-infected patients. In the present study, peripheral blood mononuclear cells (PBMCs) isolated from patients with chronic HCV or hepatitis B virus (HBV) infection were stimulated with TLR ligands to determine the production of IL-6 and IL-8 and to identify the clinical parameters associated with hyporesponsiveness to TLR ligands in patients with chronic HCV infection. The results showed that pro-inflammatory cytokine responses to TLR ligands were suppressed in PBMCs isolated from HCV-infected, but not HBV-infected, patients. The reduced cytokine responses to TLR ligands seen in HCV-infected patients correlated with platelet counts and serum prothrombin time levels. In contrast, there was no correlation between TLR-induced cytokine responses and serum levels of core antigen. Thus, hyporesponsiveness to TLR ligands in HCV-infected patients is correlated with liver dysfunction. In conclusion, both host factors and viral factors may be involved in the generation of hyporesponsiveness to TLR ligands in patients with chronic HCV infection.     

Clinical and immunological features of systemic lupus erythematosus complicated by Jaccoud's arthropathy

This work was undertaken to evaluate clinical and immunological features in patients with systemic lupus erythematosus (SLE) complicated by Jaccoud's arthropathy. Patients diagnosed with SLE between 1985 and 1999, and who met the criteria of Villiaumey et al., were checked for Jaccoud's arthropathy. Clinical features were retrospectively analysed for patients with both diseases. Sjögren's syndrome and human leukocyte antigens (HLA) in these patients were evaluated. Jaccoud's arthropathy was found in 15 (4.4%) of 340 patients with SLE. The mean age at the time of SLE diagnosis was significantly higher in these patients than in our control SLE patients, which was 51.2 ± 13.0 years (n = 15) and 29.6 ± 13.0 years (n = 222) (p = 2.1 × 10^?8). Sjögren's syndrome was diagnosed according to the European Community Study Group's criteria in 10 (91%) of 11 patients examined. The incidence of HLA-A11 (5/9, 55%) and -B61(40) (5/9, 55%) in patients with Jaccoud's arthropathy was higher in the Japanese population (A11, 17.4%, p < 0.05; B61, 17.5%, p < 0.057. Jaccoud's arthropathy in patients with SLE is associated with Sjögren's syndrome, elderly SLE, HLA-A11, and HLA-B61. These clinical features might be characteristic of patients with Jaccoud's arthropathy and SLE.