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ID PMID Title PublicationDate abstract
1372187 Cytokine regulation of colony-stimulating factor (CSF) production in cultured human synovi 1992 Mar 15 Synovial fibroblasts are likely to be a significant source of granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte-CSF (G-CSF), which could be crucial to the pathogenesis of rheumatoid arthritis. Using specific enzyme-linked immunosorbent assays (ELISAs) and Northern analysis, GM-CSF and G-CSF expression were followed in human synovial fibroblast-like cells in response to a number of agents, either alone or in the presence of an optimal stimulatory concentration of interleukin-1 (IL-1). For both CSFs, interferon-gamma (100 U/mL) did not increase their levels but dramatically suppressed the stimulatory action of IL-1, while basic fibroblast growth factor (10(-8) mol/L), although nonstimulatory by itself, potentiated IL-1 action. The glucocorticoid, dexamethasone (10(-7) mol/L), inhibited IL-1-stimulated CSF production. However, evidence was obtained for noncoordinated CSF regulation. Cyclooxygenase inhibitors potentiated the action of IL-1 on GM-CSF synthesis but suppressed G-CSF synthesis, suggesting that endogenous cyclooxygenase products can have opposite effects in modulating the levels of each CSF. Also, the lymphokine, IL-4 (250 pmol/L), slightly inhibited GM-CSF formation in the presence of IL-1 but elevated the G-CSF levels in these cultures without having an effect by itself. Transforming growth factor beta (less than or equal to 20 ng/mL) did not modulate levels of either CSF. Mesenchymal cell production of both GM-CSF and G-CSF is generally viewed as being under coordinate control; our findings suggest that their synthesis in IL-1-stimulated human synoviocytes can be modulated by a number of agents, in some cases with divergent actions depending on which CSF is examined.
8793257 Autoantibodies in black South Africans with systemic lupus erythematosus: spectrum and cli 1996 May The clinical features and autoantibody profile of 111 black South Africans (103 females and 8 males) with systemic lupus erythematosus were retrospectively analysed. The mean age of the patients was 35.1 years and mean duration of disease 3.5 years. The commonest clinical and laboratory features noted were arthritis (62.2%), hypocomplementaemia (61.2%), haematological abnormalities (60.5%) and malar rash (55%). The serological abnormalities included antinuclear antibodies (98.2%), anti-dsDNA (66.2%), anti-Sm (44.2%), anti-RNP (65.5%), anti-Ro (60.5%), anti-La (28.4%) and rheumatoid factor (10.1%). Positive clinicoserological associations observed included: combination of anti-dsDNA antibodies and low C4 levels with renal disease; anti-dsDNA antibodies with cutaneous vasculitis; anti-Sm antibodies with psychosis; anti-RNP antibodies with Raynaud's phenomenon; anti-Ro antibodies with renal disease, psychosis and malar rash. Anti-La antibodies showed a weak negative association with serositis and Raynaud's phenomenon. Most of these clinical correlates are consistent with past studies. The high frequency of anti-Sm and anti-RNP antibodies is similar to the observations in African-Americans and Afro-Caribbeans.
8777847 Autoantibodies in black South Africans with systemic lupus erythematosus: spectrum and cli 1996 Mar The clinical features and autoantibody profile of 111 black South Africans (103 females and 8 males) with systemic lupus erythematosus was retrospectively analysed. The mean age of the patients was 35.1 years and mean duration of disease 3.5 years. The commonest clinical and laboratory features noted were arthritis (62.2%), hypocomplementaemia (61.2%), haematological abnormalities (60.5%) and malar rash (55%). The serological abnormalities included antinuclear antibodies (98.2%), anti-dsDNA (66.2%), anti-Sm (44.2%), anti-RNP (65.5%), anti-Ro (60.5%), anti-La (28.4%) and rheumatoid factor (10.1%). Positive clinicoserological associations observed included: combination of anti-dsDNA antibodies and low C4 levels with renal disease; anti-dsDNA antibodies with cutaneous vasculitis; anti-Sm antibodies with psychosis; anti-RNP antibodies with Raynaud's phenomenon; anti-Ro antibodies with renal disease, psychosis and malar rash. Anti-La antibodies showed a weak negative association with serositis and Raynaud's phenomenon. Most of these clinical correlates are consistent with past studies. The high frequency of anti-Sm and anti-RNP antibodies is similar to the observations in African-Americans and Afro-Caribbeans.
8624647 The clinical need for an acute rheumatology referral service. 1996 Apr Should rheumatologists provide an acute referral service for general practitioners (GPs) and other clinical units? Is it cost effective? We prospectively studied acute referrals to one unit over 10 months, recording their source, diagnosis, management and outcome. Current rheumatology patients and cases only needing telephone advice were excluded. There were 253 referrals: 82 from GPs, nine from Accident and Emergency, and 162 from other hospital units. Their diagnoses comprised connective tissue diseases (22), back pain (46), inflammatory arthritis (59), osteoarthritis (22), paediatric cases (11), soft tissue problems (41) and 52 other disorders. Thirty-two needed active treatment within 24 h (classified as emergencies); examples included cerebral lupus, vasculitic pulmonary haemorrhage, retroperitoneal lymphoma with sacral plexus compression, temporal arteritis with reduced visual acuity and acute monoarthritis. All needed immediate therapy; only one died. Most (176 cases) were less urgent and needed advice in 48 h. Examples included osteoporotic vertebral collapse and acute rheumatoid disease. Forty-five could have been seen routinely; examples included lateral epicondylitis and adhesive capsulitis. The service required 1 day per week of medical staff time at an average cost of 45 pounds per case. We concluded that an acute rheumatology service is needed; it can be provided within the working day and is cost effective.
8088081 Pneumatosis cystoides intestinalis in systemic lupus erythematosus with intestinal vasculi 1994 Jun Pneumatosis cystoides intestinalis (PCI) is an uncommon disorder usually associated with intestinal and pulmonary obstructive diseases, recent abdominal procedures and systemic illnesses. PCI has been reported in patients with systemic lupus erythematosus associated with intestinal vasculitis. We describe herein a patient with a month history of intermittent abdominal pain, diarrhoea, hyporexia, and weight loss who underwent intestinal resection for acute abdomen. Post-operatively she gave a three-month history of arthritis of the right knee, ankles and feet, arthralgia of the wrists, MCPs and shoulders. She also described weakness, weight loss, Raynaud's phenomenon, and a skin rash. Laboratory examination revealed an increased ESR, low haemoglobin and haematocrit, positive rheumatoid factor, a positive ANA with a speckled pattern, as well antibodies to DNA, SS-A and cardiolipin. The abdominal symptomatology especially pain, cramps and bouts of diarrhoea persisted after the surgery and became worse two months later. Abdominal X-ray showed distention of bowel with cyst formation in the wall of the entire colon. A diagnosis of PCI was made radiologically. The intestinal pathology was reviewed and vasculitis was identified. The patient received treatment with high dose prednisone with an excellent response; prednisone was progressively tapered and she has been asymptomatic without abdominal complaints or other symptoms for over a year.
1604327 Regulation of the expression of adhesion molecules by human synoviocytes. 1992 Apr The capacity of synoviocytes to participate in inflammatory responses may be altered by the cytokine-enhanced expression of adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1). To examine this possibility, the ability of selected cytokines to enhance ICAM-1 expression was examined. The data indicated that each of these cytokines (interleukin-1 beta greater than tumor necrosis factor-alpha, interferon-gamma much greater than interleukin-6) can up-regulate synoviocyte ICAM-1 expression. This can potentially increase the ability of these cells to interact with infiltrating inflammatory cells, thereby propagating immunologically mediated inflammation such as occurs in rheumatoid synovitis.
1575582 Patients with systemic lupus erythematosus and Jaccoud's arthropathy: a clinical subset wi 1992 Mar Jaccoud's arthropathy is a chronic deforming synovitis occurring in a subset of patients with systemic lupus erythematosus (SLE). To evaluate whether patients with SLE and Jaccoud's arthropathy behave differently in their acute phase reaction from patients with SLE without Jaccoud's arthropathy, a prospective study was carried out on 72 consecutive patients with SLE. Patients were assessed for Jaccoud's arthropathy according to a protocol, disease activity was scored, and laboratory tests, including tests for C reactive protein, were performed. Seven patients were classified as having definite Jaccoud's arthropathy. In those patients the serum concentrations of C reactive protein were higher than in those without Jaccoud's arthropathy, whereas disease activity scores and treatment were comparable. Additionally, patients with Jaccoud's arthropathy had a longer disease duration and a longer history of arthritis than those without, whereas IgM rheumatoid factor was observed more often. The increased concentration of C reactive protein in patients with Jaccoud's arthropathy is compatible with a persistent inflammatory reaction. Serial testing of C reactive protein in combination with other laboratory parameters may be a guideline for treatment in patients with SLE and Jaccoud's arthropathy.
8376838 Poststreptococcal anti-myosin antibody idiotype associated with systemic lupus erythematos 1993 Oct Anti-myosin antibodies are found in acute rheumatic fever (ARF), a sequela of group A streptococcal infection. An antiidiotypic serum was produced that was specific for idiotopes expressed by anti-myosin antibodies in ARF (anti-My1). Studies indicated that idiotypic determinants detected with this serum were present in anti-myosin antibodies and absent from normal human immunoglobulins that lacked specificity for myosin. Anti-My1 was tested against sera from patients with other types of autoimmune diseases as well as uncomplicated streptococcal infections. Sera from systemic lupus erythematosus (SLE), Sjögren's syndrome (SS), and poststreptococcal acute glomerulonephritis patients demonstrated idiotypic reactivity with anti-My1. Affinity-purified anti-myosin antibodies from SLE, SS, and ARF sera also reacted strongly with anti-My1, indicating that immunoglobulins produced in these diseases share idiotypic determinants. The data demonstrated an association of the My1 idiotype with poststreptococcal sequelae and the two autoimmune diseases SLE and SS.
7639803 Biased T cell receptor V beta gene usage during specific stages of the development of auto 1995 Aug OBJECTIVE: To analyze the repertoire of T cell receptor (TCR) V beta gene transcribed and expressed within the autoimmune lesions of the salivary gland in the MRL/lpr mouse model of Sjögren's syndrome. METHODS: Monoclonal antibodies (MAb) were used to determine the prevalence of selected V gene elements on T cell infiltrates from salivary glands of MRL/lpr mice. To analyze TCR V beta gene usage, we used reverse-transcriptase polymerase chain reaction (RT-PCR) and single-strand conformational polymorphism (SSCP) analyses. RESULTS: A predominance of V beta 8+ T cells was detected within the inflammatory lesions during development of autoimmune disease (confirmed by flow cytometry). RT-PCR analysis revealed that in autoimmune sialadenitis, the predominant expression of the V beta 8 gene segment began in the early stages of disease (2-month-old mice) and increased over time. Extensive age-related diversity of TCR V beta gene usage was also observed. SSCP analysis demonstrated a distinct and common binding pattern of the V beta 8 gene PCR product from the cell infiltrates during the course of the disease. CONCLUSION: Our data suggest that in the MRL/lpr mouse model of Sjögren's syndrome, there is restricted usage of TCR V beta elements according to the stage of the disease, and that V beta 8 are probably used preferentially in the recognition of a single unknown self antigen in the salivary gland.
8640871 In vivo role of IL-10 and IL-12 during development of Sjögren's syndrome in MRL/lpr mice. 1996 Mar 15 Expression of local cytokine genes including interleukin 10 (IL-10) and IL-12 was analyzed in the salivary gland tissues of MRL/lpr mice with Sjögren's syndrome. We demonstrate a significant role of IL-10 and IL-12 in vivo during development of Sjögren's syndrome in MRL/lpr mice. IL-10 mRNA expression was detected before the onset of disease and was upregulated during the course of autoimmune sialadenitis by RT-PCR. A predominant level of expression of IL-12 mRNA was also detected earlier in the proinflammatory stage of autoimmune sialadenities. Moreover, MHC class II (I-Ak) mRNA was detected before the onset of inflammatory lesions until older ages in the salivary glands of MRL/lpr mice. These results suggest that endogenous IL-10 and IL-12 may play important roles on immune-mediated destruction of the salivary glands during development of organ-specific autoimmunity in MRL/lpr mice.
7750054 Lupus in Chinese male: a retrospective study of 61 patients. 1995 Feb BACKGROUND: Systemic lupus erythematosus (SLE) has traditionally been considered a disease of women, and is uncommon in men. In recent years, several large clinical series of male lupus patients have been reported. As no known data are available for lupus in males from Taiwan, a retrospective analysis of data from male lupus patients was done to determine whether these patients differed from other series of male or female SLE patients in the literature. METHODS: Sixty-one male lupus patients, diagnosed and followed in Tri-Service General Hospital, between 1983 and 1993, were studied and their data analyzed, retrospectively. RESULTS: The mean age of diagnosis was 30 +/- 17 (mean +/- SD, range: 13-81) years. The peak age of diagnosis was between 13 and 40 years. The mean duration of follow-up was 36 +/- 36 (range: 2-256) months. The 1-, 5- and 10-year survival rates were 84%, 76% and 75%, respectively. The frequency of clinical manifestations were renal disease, 75%; malar rash, 70%; arthritis, 60%; fever, 56%; photosensitivity, 48%; pleuritis, 39%; pericarditis, 31%; alopecia, 31%; mucosal ulcers, 29%; neuropsychiatric disease, 26%; discoid lupus, 21%; vasculitis, 15%; Raynaud's phenomenon, 10%; and lymphadenopathy, 2%. The frequency of abnormal laboratory findings were antinuclear antibodies (ANA), 95%; hypocomplementemia, 77%; antibodies to double-stranded DNA (anti-dsDNA), 57%; leukopenia, 44%; lupus erythematosus (LE) cells, 39%; anti-Ro, 39%; anti-Smith antibodies (anti-Sm), 19%; thrombocytopenia, 18%; rheumatoid factor, 17%; anti-ribonucleoprotein antibody (anti-RNP), 14%; autoimmune hemolytic anemia, 8%; false-positive venereal disease research laboratory test (VDRL), 6% and anti-La, 4%. CONCLUSIONS: In a review of the 61 ethnic Chinese male lupus patients, a higher frequency of renal disease, malar rash and photosensitivity, but a lower frequency of arthritis and lymphadenopathy, compared to previous reports of Caucasians. There were no significant immunological differences from other series of male lupus, except a lower frequency of anti-dsDNA. In general, poor prognosis was noted for male lupus patients here.
8632069 Cutaneous extravascular necrotizing granuloma (Winkelmann granuloma): confirmation of the 1996 May BACKGROUND: An unusual palisading granuloma has been described in patients with immunoreactive diseases. Multiple names have been given to this lesion. OBJECTIVE: Our aim was to verify whether a distinct palisading granuloma can be used as a marker for systemic disease. We also propose unifying nomenclature. METHODS: Thirty-four biopsy specimens from 22 patients were selected for study on the basis of histologic criteria. The medical histories of these patients were subsequently reviewed for clinical information. RESULTS: At least 21 of the 22 patients with cutaneous extravascular necrotizing granuloma had evidence of an underlying immunoreactive systemic illness. In each, the systemic disease preceded or was diagnosed concurrently with the cutaneous lesions. CONCLUSION: The cutaneous extravascular necrotizing granuloma has unique clinical and histologic features. In a great majority of cases, a systemic immunoreactive disease is present.
8039804 Oligoclonality of T cells in salivary glands of autoimmune MRL/lpr mice. 1994 Apr The aim of this study was to obtain further information about exocrine glandular immunopathology and the potential of the MRL/lpr strain as a model of Sjögren's syndrome. Immunoenzyme staining (ABC technique) and monoclonal antibodies defining CD3 T-cell receptor (TcR) alpha beta, gamma delta and TcR V beta 2, V beta 4, V beta 6, V beta 7, V beta 8.1,2, V beta 10b and V beta 11 were used to identify the mononuclear cells (MNC) in salivary gland infiltrates and lymph nodes of 2- and 4-5-month-old female MRL/lpr mice. TcR alpha beta + cells dominated clearly over TcR gamma delta + cells in both salivary glands and lymph nodes. In addition, to be expressed on lymphocyte-like cells, TcR gamma delta + cells also had a dendritic appearance. The frequency pattern of TcR expression in early inflammation (2 months) was V beta 8.1, 2 > V beta 6 > V beta 4 > V beta 10b > V beta 2 > V beta 7 > V beta 11. Clear differences in frequencies could be found between salivary glands and lymph nodes in established sialadenitis (4-5 months). Particularly V beta 4, V beta 8.1,2 and V beta 10b showed expansion in salivary glands at > or = 4 months. In conclusion, this study shows a diverse repertoire of TcR at local sites of MNC infiltration in autoimmune MRL/lpr mice. However, with increasing age it also shows a preferential utilization of certain V beta gene products.
7693382 Sera from patients with rheumatic diseases recognize different epitope regions on the 52-k 1993 Nov Patients suffering from systemic lupus erythematosus (SLE) or Sjögren's syndrome (SS) often contain autoantibodies directed to the Ro(SS-A) complex. In this study the antigenic determinants on two of the components of the Ro complex, i.e. the Ro60 and the Ro52 polypeptides, were investigated. Anti-Ro+ sera were selected by counter-immunoelectrophoresis. Depending on the detection method, 59-68% of the SLE patients produced anti-Ro but not anti-La antibody, while 72-81% of the SS patients produced both anti-Ro and anti-La antibody. Immunoprecipitation of recombinant Ro-proteins showed that 61 sera (87%) were reactive with both Ro proteins, seven sera with Ro60 only, one serum with Ro52 only, and one serum did not precipitate the proteins at all. The anti-Ro60 reactivity of human sera is strongly associated with the native form of Ro60, suggesting that conformational autoepitopes are an important feature of Ro60. In the case of Ro52, frequently the residues located between amino acids 216 and 292 were essential for reactivity with the antibodies. With 70% of the lupus sera tested this appeared to be the only region important for reactivity. The antibodies of SS patients generally recognized multiple B cell epitopes located between amino acids 55 and 292. The results of this study indicate that the antigenic determinants on Ro52 are different for autoantibodies produced by lupus patients compared with those of SS patients.
1586247 Antiphospholipid antibodies and HLA associations in primary Sjögren's syndrome. 1992 Apr Blood samples from 65 patients with primary Sjögren's syndrome were evaluated for the presence of antiphospholipid antibodies. Increased levels of antiphospholipid antibodies were found in 13 of 65 (20%) of patients. These antiphospholipid antibodies were predominantly of the IgA isotype, in contrast with the IgG isotype antiphospholipid antibodies found in patients with systemic lupus erythematosus (SLE). The presence of IgA antiphospholipid antibodies in the patients with primary Sjögren's syndrome was not significantly associated with arterial or vascular thrombosis, nor peripheral or central nervous system vasculitis. There was no association with laboratory determined features such as lupus anticoagulant or false positive results of the Venereal Disease Research Laboratory (VDRL) test. Oligonucleotide specific DNA amplification and hybridisation with allele specific probes was used to examine the HLA-D antigens occurring in this group of patients with primary Sjögren's syndrome. Of 13 patients with antiphospholipid antibodies, seven had the genotype HLA-DR2/DR3. However, compared with the whole group of 65 patients with Sjögren's syndrome, no increased occurrence of haplotype DR2 or DR3 was noted. These results suggest that gene interaction between DR2 and DR3 may play a part in the production of antiphospholipid antibodies in patients with Sjögren's syndrome. In contrast with patients with SLE, the IgA antiphospholipid antibodies in patients with Sjögren's syndrome are not risk factors for thrombosis or vasculitis. The presence of IgA antiphospholipid antibodies in patients with Sjögren's syndrome probably reflects its production at mucosal sites of inflammation and the absence of vasculopathy may be due to the inability of IgA antibodies to activate complement.
1611199 A case of primary biliary cirrhosis associated with Hashimoto's thyroiditis, scleroderma a 1992 Mar A 53-year-old woman was admitted because of Raynaud's phenomenon, polyarthralgia and polymyalgia. Biopsy specimens of the liver and thyroid gland revealed characteristic findings of primary biliary cirrhosis (PBC) (stage I by Scheuer's classification) and chronic thyroiditis. Her clinical features were also complicated by scleroderma (type I by Barnett's classification) and Sjögren's syndrome (Sjs) with keratoconjunctivitis sicca. Thyroid hormone replacement therapy led to improvement in thyroid function, normalization of the biliary tract enzymes and alleviation of subjective symptoms.
8864831 Increased production of B cell growth factor (BCGF) in Sjögren's syndrome. 1996 Aug The objective of this investigation to clarify possible roles of B cell growth factor (BCGF) in the abnormal activation of B cells in Sjögren's syndrome (SS). Lymphocyte subsets of peripheral blood from 20 patients with SS (14 with primary SS and six with secondary SS) and 11 healthy donors were analysed by flow cytometry. Supernatants of peripheral blood T cells obtained from patients with SS and from donors, cultured with or without PHA, were studied using bioassay with a B cell line, KS-3.F10. The number of CD20+ cells and CD4+DR+ cells was significantly increased in SS patients compared with healthy donors. T cells from SS patients showed increased production of BCGF, whether or not they were stimulated with PHA. The enhancement of BCGF production by PHA had a positive correlation with the percentage of CD4+CD45RA+ cells, and a negative correlation with the focus score of lip biopsy. Our experiments showed that BCGF production by T cells was spontaneously increased in SS patients. The accelerated BCGF production with PHA stimulation may be related to the increase of CD4+CD45RA+ cells and the decrease of the inflammation determined by the grade of cell infiltration into salivary glands, but not by the increase of CD20+ cells.
8804813 Lymphoid infiltrates of the salivary glands: pathology, biology and clinical significance. 1996 May Lymphoid infiltrates of the salivary glands are common to a variety of pathologic conditions including autoimmune disorders, malignant lymphomas, and immunoregulatory responses to parenchymal neoplasms. Clearly, the correct identification of these salivary gland lymphoid infiltrates has important implications regarding patient prognosis and management. Immunophenotypic and molecular analyses have demonstrated that many lesions formerly regarded as myoepithelial sialadentis or benign lymphoepithelial lesion in fact represent neoplastic lymphoid proliferations with the potential for extrasalivary dissemination. In the most recent classification scheme of non-Hodgkin's lymphomas, these neoplasms fall within the spectrum of low-grade B-cell lymphoma of mucosa-associated lymphoid tissue. In the early stages of HIV infection, patients may develop salivary gland enlargement resulting from cystic lymphoepithelial lesions. These lesions are thought to reflect a localized manifestation of persistent generalized lymphadenopathy. Although HIV-associated salivary gland disease is regarded as a benign condition, malignant lymphoma has been described in association with some of these lesions, and further work is required to define more precisely the risk of salivary gland lymphoma in HIV-infected patients. Tumor-associated lymphoid proliferation refers to a prominent lymphoid reaction accompanying certain epithelial tumors of the salivary glands. Although tumor-associated lymphoid proliferation has not received as much attention as other types of salivary lymphoid infiltrates, it is a common phenomenon that is sometimes mistaken for an intraparotid lymph node harboring metastatic carcinoma.
8260847 Cell-free Fc-gamma receptor III in sera from patients with systemic lupus erythematosus: c 1994 Fifty patients (41 females and 9 males, ranging in age from 12 to 79 years) with systemic lupus erythematosus (SLE) and 20 normal controls were evaluated for the presence of plasma cell-free Fc gamma receptor III (Fc gamma RIII) using an ELISA based upon a sandwich of two monoclonal antibodies. The standard curve was obtained with serial dilutions of recombinant Fc gamma RIII. In the patients, the cell-free Fc gamma RIII levels ranged from to 1.76 micrograms/ml, while it did not exceed 0.21 microgram/ml in the controls. Assuming that the cutoff is 0.25 microgram/ml, 11 SLE patients and no controls had elevated cell-free Fc gamma RIII levels in the serum. Among the SLE patients, the level of cell-free Fc gamma RIII was significantly lower (p = 0.05) in 4 patients with sicca syndrome than in the remaining 46. Furthermore, cell-free Fc gamma RIII levels appeared to be lower in 11 patients with renal involvement than in those without. For the biological parameters, we observed that the 27 patients who presented lymphopenia also had a lower level of cell-free Fc gamma RIII when compared to the 23 patients without lymphopenia (0.09 +/- 0.19 versus 0.35 +/- 0.52 microgram/ml; p = 0.05). Circulating cell-free Fc gamma RIII may originate from shedding by presumably activated polymorphonuclear cells.
1588978 Risk factors for cyclosporine-induced nephropathy in patients with autoimmune diseases. In 1992 Jun 18 BACKGROUND: Cyclosporine is an immunosuppressive drug that is used to treat patients with autoimmune disease as well as patients who have received allografts. The drug can cause renal damage, but the incidence of and risk factors for nephropathy in patients treated with cyclosporine for autoimmune or inflammatory diseases are not known. METHODS: We analyzed data from renal biopsies performed in 192 patients (129 adults and 63 children) who had been treated with cyclosporine for insulin-dependent diabetes mellitus of recent onset, uveitis, psoriasis, Sjögren's syndrome, or polychondritis. The mean (+/- SD) initial dose of cyclosporine was 8.2 +/- 2.8 mg per kilogram of body weight per day, and the duration of treatment was 4 to 39 months (median, 13). RESULTS: Forty-one patients (37 adults and 4 children) had cyclosporine-induced nephropathy, defined as at least moderate focal interstitial fibrosis with tubular atrophy, arteriolar alterations, or both. As compared with patients in whom nephropathy did not develop, these patients received a larger initial dose of cyclosporine (9.3 +/- 2.8 vs. 8.0 +/- 2.8 mg per kilogram per day), had a larger maximal increase in the serum creatinine concentration above base-line values (101 +/- 77 percent vs. 50 +/- 33 percent), and were older (31 +/- 13 vs. 23 +/- 12 years). These three variables were shown by multivariate logistic-regression analysis to be significant risk factors. The duration of the elevation in the serum creatinine concentration and the occurrence of elevated blood pressure were not additional risk factors. CONCLUSIONS: Nephropathy is an important potential effect of cyclosporine therapy. The risk of its development in patients with autoimmune diseases who are treated with cyclosporine can be minimized by allowing a dose no higher than 5 mg per kilogram per day and avoiding increases in serum creatinine of more than 30 percent above the patient's base-line value.