Increase of RP105-lacking activated B cells in the peripheral blood and salivary glands in patients with Sjögren's syndrome.

OBJECTIVE: To quantify the activated B cells in the peripheral blood and salivary glands of patients with Sjögren's syndrome (SS) by analyzing the expression of RP105 molecule on the B cells. METHODS: The expression of RP105 on the peripheral blood B cells of patients with SS (19 cases) was analyzed by flow cytometry. RP105-positive and negative B cells were sorted and cultured in vitro and the amount of immunoglobulins (IgG and IgM) produced in the supernatant was measured by enzyme-linked immunosorbent assay (ELISA). Salivary gland biopsy samples from 9 SS patients were histologically evaluated and the sequential frozen sections were separately immunostained by anti-RP105 and anti-CD20 monoclonal antibodies. RESULTS: A significantly higher proportion of peripheral blood RP105-negative B cells was found in SS patients than in healthy individuals. RP105-negative, but not positive, B cells from SS patients were capable of producing IgG and IgM spontaneously in vitro, which was enhanced by the addition of Staphylococcus aureus Cowan I strain (SAC) or IL-6. Salivary glands from 2 of 9 SS patients were found to have lymphoid follicles whose germinal centers consisted of RP105-negative B cells. Moreover, a larger proportion of B cells extensively infiltrating the area other than lymphoid follicles was also RP105-negative. CONCLUSION: RP105-negative B cells, a subset of highly activated and well differentiated B cells, which are increased in number in the peripheral blood and extensively infiltrate salivary glands, may be responsible for the production of class-switched immunoglobulin in SS. In addition, those cells might be associated with the inflammation and tissue damage of the salivary glands.

The association of Behçet's disease with myelodysplastic syndrome in Japan: a review of the literature.

OBJECTIVE: [corrected] To determine the clinical characteristics of patients with myelodysplastic syndrome (MDS)-associated Behçet's disease (BD) in Japan. METHODS: 54 Japanese cases of MDS-associated BD obtained from the literature and from our own clinical experience were reviewed. The clinical features of MDS-associated BD were compared with those of the 1991 nationwide BD survey in Japan. RESULTS: In MDS-associated BD, the average age at onset was 42.6 years, which was 6.9 years later than for all BD patients; females developed disease more frequently than males (male: female ratio = 0.80). In MDS-associated BD cases, the occurrence of eye lesions was significantly lower, the frequency of intestinal lesions was markedly higher, and the rate of HLA-B51 positivity was lower than that in all BD. BD and MDS developed nearly simultaneously in 49.0% of cases; BD preceded MDS in 31.4% of the cases. The distribution of the age at BD onset showed two peaks, one in the 3rd decade and the other in the 6th decade. Females were more likely to develop younger-onset disease, while men were more likely to develop older-onset MDS-associated BD. Furthermore, in the older-onset group, BD was diagnosed together with or after the diagnosis of MDS, while half of the younger-onset group developed BD earlier than MDS. CONCLUSION: MDS-associated BD patients form a distinct subset of patients. There may, in fact, be two major groups of MDS-associated BD patients based on age, gender, and temporal relationship of the two diseases.

Efficient isolation of mutant antigen presenting cell lines by functional selection using T cell clones.

An efficient method for the isolation of mutant antigen-presenting cell (APC) lines is described. When mixtures of transfectant APC lines TA beta z (that express A beta z/A alpha d MHC class II molecules) and hypothetical variant APC lines TA beta d (that express A beta d/A alpha d class II molecules) were cultured with and selected by autoreactive A beta z/A alpha d-restricted T cell clones, the percentage of TA beta d APC lines increased from less than 1% of the original APC mixtures to almost 100% after several cycles of selection. This increase of hypothetical variant was shown to be due to the formation of aggregates of wild-type TA beta z APC lines with A beta z/A alpha d-restricted autoreactive T cell clones that results in the inhibition of proliferation and probably killing of TA beta z APC lines. Based on this, ethyl methane sulfonate (EMS)-treated TA beta z APC lines or B-B hybridoma APC lines MW4 (that express A beta z/A alpha d and A beta z/A alpha z class II molecules) were cultured with and selected by A beta z/A alpha d-restricted autoreactive T cell clones to obtain mutant APC lines that escaped the recognition by T cell clones. After cloning, about 43% of clones examined lost the ability to stimulate T cell clones with concomitant loss of class II molecule expression. Less than 1% showed loss of stimulatory activity against T cell clones in spite of the expression of normal amounts of class II molecules. Initial analysis revealed that they include APC mutant lines with (1) altered MHC class II sequences, (2) loss of adhesion molecule expression and (3) possible impairment of the peptide loading. The method described here may provide a variety of mutant APC lines that are useful for the analysis of antigen processing and presentation pathways as well as of class II structure for T cell stimulation.

Analysis of Vbeta4 T cell receptor CDR3 repertoire in BALB/c and (NZB x NZW)F1 mice.

To examine the unique TCR repertoire in auto-immune-prone (NZB x NZW)F1 (B/WF1) mice, we analysed the Vbeta4 CDR3 region of TCRbeta chain in spleens of young (1 month old) and aged (6 month old) BALB/c and B/WF1 mice. Total RNA from spleens was used for cDNA synthesis and TCRVbeta4 PCR products were cloned and sequenced. Young B/WF1 mice showed high frequency (38.5%) of anionic amino acid residues at position beta100 in TCRVbeta4 chain compared to that (19.0%) in young BALB/c mice. Aged BALB/c mice and B/WF1 mice showed increase of frequency (38.1 and 51.9%, respectively) of anionic residues at beta100. These results indicate that Vbeta4-T cells that have anionic residues at beta100 in CDR3 region of TCRbeta chain increase with age in normal mice. Auto-immune prone mice show high frequency of anionic residues at beta100 in TCRVbeta4 chain even at the age of 1 month. These T cells may interact with cationic self-antigen(s) and might contribute to the onset and/or the progression of systemic autoimmunity in concert with other genetic elements in B/WF1 mice.

Polyangiitis overlap syndrome with eosinophilia associated with an elevated serum level of major basic protein.

Polyangiitis overlap syndrome is a new disease entity and the reported cases in the literature are still limited. We describe a female patient presenting with finger ulcers, skin eruptions, pleural effusion, interstitial pneumonia and eosinophilia. Skin biopsy showed systemic small-sized angiitis and thrombosis. She was diagnosed as having polyangiitis overlap syndrome and was successfully then treated with corticosteroid. It is also of interest that the disease activity was correlated with the number of eosinophils in peripheral blood. The measurement of the serum level of major basic protein released from eosinophils functioning as a coagulant indicated the possible association of eosinophilia with thrombosis and polyangiitis.

[A case of acute interstitial nephritis and nonoliguria acute renal failure induced by cimetidine].

Cimetidine is a histamine H2-receptor antagonist. Widely it is prescribed, and then various side effects have been increasingly recognized. Acute renal failure as a result of acute interstitial nephritis is one of the most important adverse effect. We report a case of biopsy-proven acute interstitial nephritis following cimetidine therapy. Farther more, we review other reported cases of cimetidine-induced acute interstitial nephritis, and discuss the clinical features and a role of immunological mechanisms of these cimetidine-induced disorders. A 52-year-old woman was admitted because of fever and protenuria. A month before admission, she developed gastric ulcer and was given cimetidine 600mg orally a day by a near physician. Laboratory data on admission included the following: white blood cell count, 14700/microliters; eosinophils, 6%; BUN, 50.7mg/dl; Cr, 7.6mg/dl; CRP, 34.0mg/dl. All drugs were discontinued because we suspected drug-induced acute renal failure, especially by cimetidine. Renal biopsy performed on day 3 showed interstitial nephritis with lymphocyte infiltration which was composed mainly of T cell. T4/T8 ratio was determined to be 1. There was neither predominance of helper nor cytotoxic cells in T cell subpopulation. We reviewed 22 cases reported and discussed the features of cimetidine-induced interstitial nephritis. The most important thing is to monitor renal function periodically with the suspicion of this disorder. On the detection of abnormality of laboratory data, cimetidine should be discontinued.

[Autoimmune hepatitis associated with mixed connective tissue disease: report of a case and a review of the literature].

A case is reported of a 29 year old female who had autoimmune hepatitis associated with mixed connective tissue disease (MCTD). The patient developed MCTD at the age of 19, and was treated with prednisolone. Liver dysfunction developed 7 years later, which exacerbated shortly after the patient suffered intrauterine fetal death during the second trimester of pregnancy. Laboratory data showed negative anti-hepatitis C antibody and hepatitis B antigen, but positive anti-smooth muscle antibody. A liver biopsy showed chronic active hepatitis. Referring to the criteria we diagnosed her as having autoimmune hepatitis. Although hepatomegaly is sometimes observed in MCTD patients, only 5 cases of autoimmune hepatitis associated with MCTD have been reported in the past. In our case, it is of note that autoimmune hepatitis developed while symptoms of MCTD were in remission, and that autoimmune hepatitis exacerbated with the emergence of anti-smooth muscle antibody following the termination of pregnancy.

[A case of Sjögren's syndrome complicated by polymyositis and sarcoidosis with HLA-B7 and DR 8: common causes of susceptibility for these diseases].

We describe a case of a Japanese patient initially presenting with Sjögren's syndrome who later developed polymyositis and sarcoidosis. A 67-year-old woman with a 4 month history of myalgia was admitted in April 1998 for examination. The patient had a 10 year history of symptoms consistent with Sjögren's syndrome. A diagnosis of polymyositis was made based on a biopsy of the muscle and an electromyogram. Positive Shirmer and Rose Bengal tests and results of a minor salivary gland biopsy were all consistent with Sjögren's syndrome. Chest computed tomography detected a bilateral hilar lymphadenopathy. Microscopic examination of a mediastinal lymph node demonstrated multiple noncaseating granulomas with multiple epithelioid cells and Langhans-like giant cells. A diagnosis of sarcoidosis was made based on these findings. Hepatitis C infection was also detected by elevated antibody levels. The patient was given 40 mg/day of oral prednisolone and a remission of her myositis and lymphadenopathy was obtained. The patient exhibited HLA-B7 and HLA-DR 8. HLA-DR 8 is commonly associated with these three disorders, and HLA-B7 is also associated with overlap syndrome in Japanese patients. The present case suggested the possibility of a common etiological background for these three disorders. Furthermore, the importance of genetic background, including HLA phenotype, in determining susceptibility to these disorders was demonstrated.

Increased RP105-Negative B Cells in IgG4-Related Disease.

Four patients with IgG4-related disease (IgG4-RD) showed increased percentages of RP105-negative B cells in the peripheral blood. Case 1: A 66-year-old man having retroperitoneal fibrosis had 18.8% of RP105-negative B cells. Oral prednisolone improved the affected lesions and the percentage of RP105-negative B cells decreased (3.2%) after the treatment. Case 2: A 53-year-old man with retroperitoneal fibrosis had 27.9% of RP105-negative B cells. Case 3: A 38-year-old man with follicular hyperplasia showed increased percentage of RP105-negative B cells (8.3%). Case 4: A 60-year-old man with interstitial nephritis had 27.5% of RP105-negative B cells. The treatment decreased the numbers of RP105-negative B cells. Increased numbers of RP105-negatvie B cells is possibly associated with disease activity of IgG4-RD. Analysis of expression of RP105 on B cells may be helpful in evaluation of disease activity of IgG4-RD.

Ex vivo CD(+) T-cell cytokine expression from patients with Sjögren's syndrome following in vitro stimulation to induce proliferation.

OBJECTIVE: To assess ex vivo CD4(+) T-cell cytokine expression from patients with primary Sjögren's syndrome (SS) following in vitro stimulation to induce proliferation, as proliferation is closely related to differentiation of cytokine-producing cells. METHODS: Peripheral blood mononuclear cells (PBMCs) separated from primary SS patients (n = 28) and controls (n = 25) were analysed. PBMCs were stimulated with concanavalin A followed by phorbol 12-myristate 13-acetate and ionomycin. Intracellular interferon-gamma (IFN-gamma) and interleukin-4 (IL)-4 in proliferating CD4(+) T cells were assessed by flow cytometry. The proportion of cytokine-producing cells and proliferating cells in each division cycle was assessed using [5(and 6)-carboxyfluorescein diacetate, succinimidyl ester]-labelled CD4(+/-) T cells. RESULTS: The proportion of IFN-gamma+ proliferating CD4(+) T cells in each cell division cycle from extraglandular SS was increased in glandular SS patients compared glandular SS patients with controls (P<0.05 approximately 0.01). The percentage of IFN-gamma single positive proliferating CD4(+) T cells was greater in extraglandular SS patients (26.7+/-14.1%) compared with glandular SS (9.9 +/- 9.1%) (P<0.01) and controls (9.4 +/- 5.8%) (P<0.001). There was no significant difference in the percentages of IL-4(+) proliferating CD4(+) T cells among the groups. However, the proliferating response of CD4(+) T cells was significantly decreased in extraglandular SS patients (percentage of proliferating cells 38.4 +/- 18.6%) compared with that in glandular SS patients (64.2 +/- 17.2%) (P<0.05) and controls (63.1+/-10.6%) (P<0.01). CONCLUSIONS: CD4(+) T cells from extraglandular SS patients may have a predisposition for entry into the IFN-gamma-producing effector pathway as a result of the stimulations. These results are helpful for understanding the immunological difference between glandular and extraglandular SS and the mechanisms of disease progression.

Prevention of steroid-induced osteonecrosis of femoral head in systemic lupus erythematosus by anti-coagulant.

Although osteonecrosis of femoral head (ONF) is one of the serious complications in systemic lupus erythematosus (SLE) associated with corticosteroid therapy, there has been few trials of prevention of ONF described. We aimed to prevent ONF in steroid-treated SLE patients using anticoagulant, warfarin, conducting a multicenter prospective study. Sixty newly diagnosed SLE patients requiring 40 mg/day or more prednisolone were alternately assigned to either of two groups; a warfarin group and a control one. Warfarin (1 to approximately 5 mg/day) was started together with the beginning of steroid therapy and continued at least for three months. Patients were observed for the development of silent ONF by magnetic resonance imaging (MRI) and symptomatic ONF by plain radiography for over five years. The warfarin group consisted of 31 patients (62 hips) and the control one 29 patients (58 hips). Silent ONF developed in 13 hips (21%) and 19 hips (33%) in the warfarin group and the control group, respectively (P = 0.13). On the other hand, warfarin tended to prevent symptomatic ONF; only three hips of 62 (4.8 %) in the warfarin group and eight hips of 58 (14%) in the control group (P = 0.08) developed silent ONF. It was also found that silent ONF developed, if it did, very early; within three months in 16 of 18 patients (89%). Among risk factors for silent ONF, steroid pulse therapy was most outstanding and it seemed to overcome the effect of warfarin. Taken together, for the time being, anti-coagulant therapy, if not significantly sufficient, may be of use for the prevention of steroid-induced ONF in SLE. We consider that this study added to important evidence for the pathogenesis and prevention of ONF.

Very early development of steroid-associated osteonecrosis of femoral head in systemic lupus erythematosus: prospective study by MRI.

The objective of this study was to define prospectively the early development of corticosteroid-induced osteonecrosis of femoral head (ONF) in patients with systemic lupus erythematosus (SLE) and to identify the association of initial steroid treatment with the development of early (silent) ONE Forty-five patients who were newly diagnosed as having SLE and required 40 mg/day or more prednisolone were enrolled. To detect silent ONF, examinations using magnetic resonance imaging (MRI) were done three months after starting steroid therapy, followed by every year's MRI and plain radiography for over five years. Clinical and laboratory data were compared between silent ONF and non-ONF groups. Of 45 patients, 15 (33%) developed silent ONF and five (11%) symptomatic ONE It was of interest that MRI detected silent ONF very early (by three months) in 14 patients (93%). It should be noted that pulse therapy with 1000 mg/day methylprednisolone was found to be done very frequently (13 of 15, 87%) in the silent ONF group compared to non-ONF group (11 of 30, 37%) (P < 0.01) although other clinical features were not significantly different between both groups. High dose corticosteroids caused elevation of serum levels of total cholesterol, albumin, and leukocyte count in most of patients. The degree of elevation of those parameters at one or three months was more prominent in the silent ONF group. In particular, the change ratio of total cholesterol at one month was outstanding in the silent ONF group compared to non-ONF group (0.551 versus 0.374, P < 0.05). In conclusion, pathological ONF develops very early in one-third of SLE patients who received high dose corticosteroids and steroid pulse therapy could be a significant risk factor. An abrupt elevation of serum total cholesterol and/or sensitivity to steroids seem to be associated with the pathogenesis of ONF.

Increased entry into the IFN-gamma effector pathway by CD4+ T cells selected by I-Ag7 on a nonobese diabetic versus C57BL/6 genetic background.

IFN-gamma-mediated Th1 effects play a major role in the pathogenesis of autoimmune diabetes in nonobese diabetic (NOD) mice. We analyzed functional responses of CD4(+) T cells from NOD and B6.G7 MHC congenic mice, which share the H2(g7) MHC region but differ in their non-MHC genetic background. T cells from each strain proliferated equally to panstimulation with T cell lectins as well as to stimulation with glutamic acid decarboxylase 524-543 (self) and hen egg lysozyme 11-23 (foreign) I-A(g7)-binding peptide epitopes. Despite comparable proliferative responses, NOD CD4(+) T cells had significantly increased IFN-gamma intracellular/extracellular protein and mRNA responses compared with B6.G7 T cells as measured by intracellular cytokine analysis, time resolved fluorometry, and RNase protection assays. The increased IFN-gamma production was not due to an increase in the amount of IFN-gamma produced per cell but to an increase in the number of NOD CD4(+) T cells entering the IFN-gamma-producing pathway. The increased IFN-gamma response in NOD mice was not due to increased numbers of activated precursors as measured by activation/memory markers. B6.G7 lymphoid cells demonstrated an absolute decrease in IFN-gamma mRNA, an increase in IL-4 mRNA production, and a significantly decreased IFN-gamma:IL-4 mRNA transcript ratio compared with NOD cells. CD4(+) T cells from C57BL6 mice also showed significantly decreased IFN-gamma production compared with CD4(+) T cells from NOD.H2(b) MHC-congenic mice (which have an H2(b) MHC region introgressed onto an NOD non-MHC background). Therefore, the NOD non-MHC background predisposes to a quantitatively increased IFN-gamma response, independent of MHC class II-mediated T cell repertoire selection, even when compared with a prototypical Th1 strain.

Increased entry of CD4+ T cells into the Th1 cytokine effector pathway during T-cell division following stimulation in Behcet's disease.

OBJECTIVES: To investigate the relationship between the production of Th1/Th2 cytokines and cell kinetics, cell division and proliferation in patients with Behçet's disease (BD). METHODS: Peripheral venous blood was drawn from patients with BD (n = 24; 10 patients with active and 14 patients with inactive BD) and normal subjects (n = 22). Peripheral blood mononuclear cells were separated immediately and were cultured with concanavalin A (Con A) followed by phorbol 12-myristate 13-acetate and ionomycin (PMA+Ion). Intracellular cytokine production of interferon-gamma (IFN-gamma) (Th1) and IL-4 (Th2) in CD4(+) T cells was determined by flow cytometry. Furthermore, CD4(+) T cells labelled with CFSE [5 (and 6) carboxyfluorescein diacretate, succinimidyl ester] were stimulated and the cells were analysed for entry into the cytokine production effector pathway during cell division in active BD and normal subjects. RESULTS: In active BD, enhanced entry into the Th1 response effector pathway of CD4(+) T cells was observed after stimulation with Con A followed by PMA+Ion. Analysis of CD4(+) T cells at an identical cell division number in response to Con A followed by PMA+Ion revealed that IFN-gamma-producing cells were increased in active BD patients compared with normal subjects. These results suggest that the Th1 response of dividing CD4(+) T cells is predominantly operating in active BD. Dividing CD4(+) T cells stimulated with Con A followed by PMA+Ion showed a phenotype of activated effector memory T cells (CD45RA(low), CD45RO(+), CD69(high)). CONCLUSIONS: Cell kinetics play a crucial role in Th1 cell differentiation and pathophysiology in BD.

Flexor tenosynovitis of the hands as an initial manifestation of systemic lupus erythematosus.

Abstract We describe a patient who presented with flexion contractures of the bilateral fingers due to tenosynovitis of the flexor digitorum tendons as an initial manifestation of systemic lupus erythematosus (SLE). A 17-year-old woman had abrupt onset of diffuse swelling and flexion contractures in the bilateral fingers, accompanied by polyarthritis and cervical lymphadenopathy. Magnetic resonance imaging (MRI) showed flexor tenosynovitis of the hands. A diagnosis of SLE was made by immunological and hematological tests, and treatment with oral corticosteroids resulted in a rapid and complete disappearance of the flexion contractures.

A mutational analysis of the Abetaz/Aalphad major histocompatibility complex class II molecule that restricts autoreactive T cells in (NZBxNZW)F1 mice. The critical influence of alanine at position 69 in the Aalphad chain.

Autoimmune symptoms of (NZBxNZW)F1 (H-2d/z) mice are reported to be critically related to the heterozygosity at the H-2 complex of the murine major histocompatibility complex (MHC). We previously showed that several Abetaz/Aalphad MHC class II molecule-restricted autoreactive T-cell clones from B/WF1 mice were pathogenic upon transfer to preautoimmune B/WF1 mice. In this study, to identify the crucial amino acid residues in Abetaz/Aalphad molecules for T-cell activation, we generated a panel of transfectant cell lines. These transfectant cell lines express the Abetaz/Aalphad MHC molecules with a mutation at each residue alpha11, alpha28, alpha57, alpha69, alpha70, alpha76 of Aalphad chain and beta86 of Abetaz chain. Replacing alpha69 alanine with threonine, valine or serine completely eliminated the ability to stimulate autoreactive T-cell clones without affecting the ability to present foreign antigen keyhole limpet haemocyanin (KLH) or L-plastin peptide to specific T-cell clones. Replacing beta86 valine with aspartic acid resulted in a decrease in the stimulation for antigen-reactive as well as autoreactive T-cell clones. Substitutions at other residues had minimal or no effect on the stimulation of either auto- or antigen-reactive T-cell clones. These results suggest that alanine at residue 69 of the Aalphad chain is critical for the activation of autoreactive Abetaz/Aalphad-restricted T-cell clones. Possible explanations for this are discussed.

Peptide-binding motifs of the mixed haplotype Abetaz/Aalphad major histocompatibility complex class II molecule: a restriction element for auto-reactive T cells in (NZBxNZW)F1 mice.

We previously showed that the mixed haplotype Abetaz/Aalphad major histocompatibility complex (MHC) class II molecules function as restricting element for autoreactive T-cell clones derived from autoimmune prone (NZBxNZW)F1 (B/WF1) mice. Subsequent analysis revealed that some of these Abetaz/Aalphad-restricted autoreactive T-cell clones were pathogenic upon transfer to pre-autoimmune B/WF1 mice. In this paper, we analysed the peptide-binding motif of Abetaz/Aalphad class II molecules. Amino acid-sequencing analysis of peptides eluted from purified Abetaz/Aalphad molecules revealed several sequences, including one that corresponds to murine l-plastin 588-601. Synthetic 18-mer l-plastin 588-605 peptide (SMARKIGARVYALPEDLV, as described by the amino acid single letter code) was demonstrated to bind to Abetaz/Aalphad MHC class II molecules on transfectant B lymphoma cells (TAbetaz). A competitive binding inhibition assay using truncation peptides revealed the core sequence for binding resides in 591Arg to 601Pro. Binding inhibition assay using substitution peptides, each having substitution to the other 19 residues at positions from 590Ala to 601Pro, revealed four major anchor sites 592Lys (p1), 594Gly (p3), 595Ala (p4), 597Val (p6) and one minor anchor site 600Leu (p9). Positively charged residues are not allowed at p3 and negatively charged residues are not allowed at p4 and p6. Relatively large hydrophobic residues (Leu, Ile) are not tolerated at p3 and p4. Met and Trp are not tolerated at p6. Based on these findings, the characteristics of peptides recognized by autoreactive T cells in B/WF1 mice are discussed.

In vivo induction of IgG anti-DNA antibody by autoreactive mixed haplotype A beta z/A alpha d MHC class II molecule-specific CD4+ T-cell clones.

We characterized autoreactive T-cell clones derived from (NZB x NZW)F1 (B/WF1) mice. These autoreactive T-cell clones are shown to be CD4+ by immunofluorescence staining and to belong to Th2 type by cytokine release assay. Specificity analysis revealed the existence of mixed haplotype A beta z/A alpha d major histocompatibility complex (MHC) class II molecule-specific T-cell clones as well as A beta z/A alpha z- or A beta d/A alpha d-specific T-cell clones. Some but not all of the mixed haplotype A beta z/A alpha d-specific autoreactive T-cell clones showed strong activity to induce IgG anti-DNA antibody production upon transfer to young (4-month-old) B/WF1 mice, indicating that T cells with these specificities might be involved in B/WF1 autoimmunity.

Retinal findings in systemic sclerosis: a comparison with nailfold capillaroscopic patterns.

OBJECTIVE: To determine the prevalence of retinal disease in systemic sclerosis (SSc) and to characterise the findings of retinopathy. Additionally, to analyse the association of retinal disease with other clinical/laboratory findings, particularly the findings of nailfold capillaries in patients with SSc. METHODS: Photographs of the ocular fundi were taken and were evaluated by an ophthalmologist who was unaware of the SSc status of the patients. The nailfold capillaries were analysed with a dermatoscope. Patients were divided into two groups according to the presence (group A) or absence (group B) of retinal disease. RESULTS: Retinal findings of the patients with SSc consisted of hard exudates, vascular tortuosity, microhaemorrhage, and macular degeneration. The prevalence of retinal disease among the patients with SSc was 34% (10/29), compared with 8%(3/38) among the controls (p=0.011). The mean systolic blood pressure and the age of the patients in group A were significantly higher than those in group B. However, there was no significant difference in the nailfold capillary damage between groups A and B. CONCLUSION: Retinal abnormalities are often seen in patients with SSc and they may reflect the vascular changes characteristic of SSc. However, retinal changes may differ in quality from the changes of nailfold capillaries.

Retinal disease in patients with systemic lupus erythematosus.

OBJECTIVE: To investigate the incidence of retinopathy in systemic lupus erythematosus (SLE) and to clarify its significance in relation to other clinical manifestations. METHODS: A cross sectional study on lupus retinopathy was made in 69 patients with SLE. One expert ophthalmologist examined the ocular fundi of the lupus patients without any information of their disease state. Clinical and laboratory findings in the patients with retinopathy and those without were compared. RESULTS: Retinopathy was found in 7/69 (10%) patients. The findings included haemorrhages, vasculitis, cotton wool spots, and hard exudates, all of which were considered to reflect vascular damage. Retinopathy was found to be associated with the presence of anticardiolipin antibody (p<0.05) and with central nervous system lupus (p<0.01). The patients with retinopathy had higher levels of serum creatinine than the patients without retinopathy (p<0.01). The disease activity of lupus, as assessed by the maximum SLE disease activity index (SLEDAI) score of the patients, was also significantly higher in the patients with retinopathy (p<0.03). CONCLUSION: Incidence of retinopathy in SLE was similar to that in previous reports and it may reflect tissue microangiopathy, particularly associated with vasculitis or anticardiolipin antibodies, or both.