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Deep learning has emerged as the leading method in machine learning, spawning a rapidly growing field of academic research and commercial applications across medicine. Deep learning could have particular relevance to rheumatology if correctly utilized. The greatest benefits of deep learning methods are seen with unstructured data frequently found in rheumatology, such as images and text, where traditional machine learning methods have struggled to unlock the trove of information held within these data formats. The basis for this success comes from the ability of deep learning to learn the structure of the underlying data. It is no surprise that the first areas of medicine that have started to experience impact from deep learning heavily rely on interpreting visual data, such as triaging radiology workflows and computer-assisted colonoscopy. Applications in rheumatology are beginning to emerge, with recent successes in areas as diverse as detecting joint erosions on plain radiography, predicting future rheumatoid arthritis disease activity, and identifying halo sign on temporal artery ultrasound. Given the important role deep learning methods are likely to play in the future of rheumatology, it is imperative that rheumatologists understand the methods and assumptions that underlie the deep learning algorithms in widespread use today, their limitations and the landscape of deep learning research that will inform algorithm development, and clinical decision support tools of the future. The best applications of deep learning in rheumatology must be informed by the clinical experience of rheumatologists, so that algorithms can be developed to tackle the most relevant clinical problems., (© 2022 The Authors. Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Importance: Rheumatic immune-related adverse events (irAEs) occur in approximately 10-20% of anti-programmed death 1 (anti-PD1)-treated cancer patients. There are limited data on the natural history, optimal treatment and long-term oncological outcomes of patients with rheumatic irAEs., Objective: The objective of the study was to describe the spectrum and natural history of rheumatic irAEs and the potential impact of rheumatic irAEs and immunomodulators on anti-PD1 tumour efficacy., Methods: Cancer patients with pre-existing rheumatic disease before anti-PD1 therapy or de novo rheumatic irAEs on anti-PD1 therapy were retrospectively reviewed across three sites. Patient demographics, treatment history, anti-PD1 irAEs, and anti-PD1 responses were evaluated. Relationships between the development or pre-existence of rheumatic irAE, use of immunomodulatory agents and outcomes were evaluated., Results: This multicenter case series describes 36 cancer patients who had rheumatic disease before anti-PD1 therapy (n = 12) or developed de novo rheumatic irAEs (n = 24). Thirty-four of the 36 patients sustained rheumatic irAEs (median time to rheumatic irAE: 14.5 weeks), including 24 de novo (18 inflammatory arthritis, three myositis, two polymyalgia rheumatica, one fasciitis) and 10 flares in 12 patients with pre-existing rheumatic disease. Corticosteroids were used in 30 of 36 patients (median duration: 10 months), and disease-modifying antirheumatic drugs were used in 14 of 36 patients (median duration: 5.5 months). The objective response rate to anti-PD1 therapy was 69% (n = 25/36) overall and 81% (n = 21/26) in the melanoma subgroup., Conclusions: Rheumatic irAEs are often chronic and require prolonged immunomodulatory therapy. Prospective studies are required to define optimal management of rheumatic irAEs that maintain long-term anticancer outcomes., (Crown Copyright © 2018. Published by Elsevier Ltd. All rights reserved.)

Competing Interests: David Liew attended Editorial Executive Committee meetings as the clinical pharmacology registrar for Australian Prescriber in 2017. He is supported by the Ronald John Gleghorn Bursary through the University of Melbourne.

Antiphospholipid syndrome is an autoimmune condition, characterised by the persistent presence of antiphospholipid antibodies and either thrombosis or obstetric morbidity. The cornerstone of therapy is long-term anticoagulation to reduce morbidity and mortality; however, better understanding of the immunological pathways may direct us to develop future therapeutic strategies. We provide an overview of the current understanding of the immunopathogenesis of this perplexing condition and its associated morbidities and current evidence for some of the immunotherapeutic strategies., (© 2017 Royal Australasian College of Physicians.)

Polymyalgia rheumatica (PMR) is a chronic inflammatory disorder of unknown cause characterised by the subacute onset of shoulder and pelvic girdle pain, and early morning stiffness in men and women over the age of 50 years. Due to the lack of a gold standard investigation, diagnosis is based on a clinical construct and laboratory evidence of inflammation. Heterogeneity in the clinical presentation and disease course of PMR has long been recognised. Aside from the evolution of alternative diagnoses, such as late-onset rheumatoid arthritis, concomitant giant cell arteritis is also recognised in 16-21% of cases. In 2012, revised classification criteria were released by the European League Against Rheumatism and American College of Rheumatology in order to identify a more homogeneous population upon which future studies could be based. In this article, we aim to provide an updated perspective on the pathogenesis and diagnosis of PMR, with particular focus on imaging modalities, such as ultrasound and whole body positron emission tomography/computed tomography, which have advanced our current understanding of this disease. Future treatment directions, based on recognition of the key cytokines involved in PMR, will also be explored., (© 2015 Royal Australasian College of Physicians.)

Intravascular large B cell lymphoma (IVLBCL) is a rare cause of pyrexia of unknown origin. Because of its protean clinical manifestations, diagnosis is elusive and is often made postmortem. We report here a case of IVLBCL that evaded diagnosis despite multiple investigations in vivo for pyrexia of unknown origin over a 5‐month period.

An increase in reports of systemic lupus erythematosus (SLE) related to tumour necrosis factor inhibitor (TNFi) therapy has recently been highlighted. We report new-onset SLE in a 22-year-old woman after 13 months of infliximab for ankylosing spondylitis (AS). Lupus symptoms promptly resolved and serologic abnormalities improved after infliximab was ceased. A flare of AS symptoms after 2 months prompted cautious introduction of an alternative TNFi, etanercept. At 14 months follow-up, neither clinical nor serologic flare of lupus had occurred. To our knowledge, this is the third reported case of infliximab-related lupus that did not recur on switching to an alternative TNFi.

Tumour necrosis factor inhibitor (TNFi) therapy, either intravenous (IV) or subcutaneous (SQ), demonstrates similar efficacy in ankylosing spondylitis (AS). The objective of this study was to examine factors influencing patient preference of TNFi. Fifty-nine (79.7%) participants were male with mean age 43.9 years and disease duration of 22.0 years. Fifty-nine patients (79.7%) agreed with the statement 'My doctor gave me a choice and I made a decision based on my personal preference'. Patients commenced first on IV TNFi most commonly cited reduced frequency of injections (96.6%), administration by a trained professional (89.7%) and use of infusion time for leisure activities (86.2%). Patients commenced on SQ TNFi cited flexibility with timing of treatment (80%), shortened administration time (73.3%) and the convenience of home therapy (73.3%). Shared clinical decision-making between clinicians and patients may be desirable for AS patients commencing TNFi therapy.

Prevalence of dietary complementary and alternative medicine (CAM) and consultation with a CAM practitioner was examined in a cross-sectional study of 75 AS patients. Seventy one of 75 (94.7%) study participants reported previous or current CAM use. Among these AS patients, 44 (72.1%) reported dietary CAM use and 27 (36.0%) were seeing a CAM practitioner at the time of study. Of 89 dietary CAM, 50 (56.4%) were perceived to be of slight or no benefit, and only 10 (11.2%) were initiated by a CAM practitioner. Compared with non-users, current dietary CAM users were more likely to be female (OR 6.5; 95% CI, 1.8-23.9). Patients attending a CAM practitioner were more likely to have university education (OR 5.7; 95% CI, 1.5-21.9) and higher BASDAI (OR 1.3; 95%CI, 1.0-1.7). Despite low rates of perceived benefit, dietary CAM use and CAM practitioner attendance is common among AS patients.

Background: The purpose of this study was to characterize an Australian cohort of ankylosing spondylitis (AS) patients and examine predictors of important disease outcomes., Methods: Cross-sectional study of first visit data among patients referred to the Austin Spondylitis Clinic from rheumatology or general practices. We obtained clinical and laboratory data and validated composite indices through self-reported questionnaire., Results: Delay in AS diagnosis averaged 8.1 years and was higher among women and younger-onset disease. Cervicothoracic mobility was better in women although they showed more entheseal tender points and greater impairment of quality of life. Those with long-standing AS had similar disease activity to recent onset disease but had greater functional disability. Current smoking was associated with worse outcomes although there was no association between cumulative exposure and AS outcomes., Conclusion: The clinical expression of AS in this first-described Australian cohort is similar to previously described cohorts. We observed greater cervicothoracic mobility and a higher enthesitis index among women perhaps contributing to longer delay to diagnosis.

Soluble low-affinity receptors for IgG are known to inhibit immune complex (IC)-mediated inflammation, and expression by leukocytes is elevated in several inflammatory diseases. Immunoglobulin M (IgM) rheumatoid factors (RF), anti-Fc autoantibodies, are found in autoimmune diseases, such as rheumatoid arthritis (RA), as well as in normal immune responses. This study demonstrated that soluble FcgammaRIIa inhibits the interaction of rheumatoid factors with ICs. The recombinant soluble low-affinity FcgammaR, rsFcgammaRIIa, partially inhibited (30-70%) the rate of precipitation of soluble ICs by RF-positive RA sera. This required the normal interaction of FcgammaRIIa with Fc as the effect could be abrogated with the Fab fragment of the blocking mAb IV-3. Furthermore, rsFcgammaRIIa partially inhibited (40%) the binding of a monoclonal IgM RF (RF-AN) to an IC formed by IgG2 antibody binding to an antigen-coated biosensor chip. Since RF-AN has been characterized by crystallography to bind to the CH2/CH3 interface of the IgG-Fc, and leukocyte FcgammaRIIa binds to a distinct site centred on the lower hinge, this inhibition is uncompetitive. Some inhibition (15%) of staphylococcal protein A binding to IC was also observed. As soluble FcgammaRIIa disrupts Fc:Fc interactions in IgG-ICs, we propose that this alteration of the IC also reduces the accessibility of Fc portions in the IC, resulting in the partial inhibition of ligands, particularly IgM RF, which bind Fc. We propose that the high concentrations of soluble FcgammaR found during inflammation can affect the properties of ICs and their interaction with the immune system.

The ELISA for detection of anti-phosphatidylethanolamine antibodies in patients with lupus anticoagulant was studied. The influence of microtitre plate types, antigen concentration, antibody dilution, and buffer system was evaluated. Human albumin in the blocking buffer gave greater numbers of positive plasma samples than bovine serum. Comparison of simultaneous plasma and serum samples showed only minor variation in binding characteristics.

Background: The finding that lupus anticoagulant (LA) is significantly associated with anti-phosphatidylethanolamine (PE) activity has led to great interest in its relation to the clinical features of the antiphospholipid syndrome (APS). Considerable variability has, however, been reported in the prevalence of anti-PE antibodies in APS patients using enzyme-linked immunosorbent assay (ELISA) methodology. The lack of standardization and differences in technique may in part explain these discrepancies. PE binds variably to different types of microtiter wells, reflected in the consequent detection, or lack of detection, of anti-PE antibodies. This study describes the use of flow cytometry as an alternative method for the detection of anti-PE antibodies., Methods: Six LA-positive plasma samples were used in this original study. Polystyrene beads were coated with PE overnight. These were subsequently incubated with patient plasma. Both IgG and IgM binding were detected by flow cytometry using a cocktail of fluorescently labelled anti-human Ig isotypes., Results: When these results were compared with those from ELISA, flow cytometric analysis provided an apparent enhanced detection of anti-PE antibodies. It was found that 6/6 were IgM anti-PE positive by flow cytometry, whereas 5/6 were IgM by ELISA; 2/6 negative for anti-cardiolipin antibodies by ELISA were positive by flow cytometry; and 2/6 positive for antiphosphatidylcholine antibodies in cytometry were negative by ELISA., Conclusions: With appropriate quantification, this method may be more sensitive than ELISA in detecting anti-PE antibodies in plasma samples of patients with APS.

Objective: To assess the phospholipid specificity of lupus anticoagulants (LAC) in autoimmune and drug induced LAC positive patients, and to determine their relevance with the clinical feature thrombosis., Methods: Thirty-five plasma samples with LAC were tested. Of these, 22 samples were from patients with autoimmune disease: 12 had systemic lupus erythematosus (SLE) and 10 primary antiphospholipid syndrome (APS). These were compared with 13 patients with drug induced LAC. Antiphospholipid (aPL) activity was tested by inhibition of LAC activity in a modified coagulation assay using the phospholipids: egg phosphatidylethanolamine (PE), 20% phosphatidylserine/80% phosphatidylcholine (PS/PC), and 15% PS/65%PC/20%PE mixture. Anticardiolipin antibodies (aCL) were measured in all samples by ELISA., Results: In the autoimmune group, 95% were positive for reactivity to PE, 68% for PS/PC, 68% for PS/PC/PE, and 77% aCL. Of the drug induced group, 69% were positive for reactivity to PE, but only 23% for PS/PC, 46% PS/PC/PE, and 23% aCL positive. In the autoimmune patient group, 64% had thrombotic episodes, all of which had anti-PE activity, and 64% had associated anti-PS activity. No drug induced patient had episodes of thrombosis., Conclusion: Autoimmune induced LAC may contain a broader range of phospholipid specificities than those from drug induced patients. These data thus identify another potential reason why patients with drug induced LAC appear to be at less risk of developing APS than those with autoimmune LAC.

Aims: To compare methodological aspects of the impact of different classification procedures used in three phases of a twin study examining genetic factors in the aetiopathogenesis of rheumatoid arthritis (RA)., Methods: We have previously reported the results of a study of the aetiopathogenesis of RA based on the Australian Twin Registry (ATR). In the original 258 pairs self-reporting a diagnosis of RA in twin, co-twin or both, a very high false positive self-reporting rate for RA was noted (Phase 1). Subsequent diagnostic information obtained by a disease-specific questionnaire, followed by telephone interviews with subjects and review of information obtained by mail and telephone interview from the patient's general practitioner or musculoskeletal specialist, identified 23 'true' RA pairs (Phase 2). Pairwise concordance percentages for RA based on those 20 discordant and 3 concordant pairs were as follows: monozygotic (MZ) 21% (95% confidence interval (CI)=6-44%), dizygotic (DZ) 0% (95% CI=0-25%) (probandwise concordance MZ 35% (8.9-67.3), DZ 0% (0-50.3)). Given the potential effects of misclassification on data interpretation, we have further pursued the accuracy of diagnosis by a systematic clinical, serological and radiographical evaluation of the 23 RA pairs (Phase 3)., Results: In only one instance did more intense diagnostic investigation of the 23 pairs result in recategorization. The probandwise concordance percentages were recalculated: MZ=37.5%, DZ=0%., Conclusions: Our original contention that genetic factors play some part in the aetiopathogenesis of RA, but do not account entirely for its determination, has been substantiated at a higher level of confidence and at almost identical levels of concordance.

In this study of antineutrophil cytoplasmic antibody (ANCA)-associated diseases, we determined the prevalence of other autoantibodies and the antigen specificities of ANCA. ANA were common, occurring in 7 of 36 (19%) patients with Wegener's granulomatosis, in 16 of 34 (47%) patients with microscopic polyarteritis, in 6 of 11 (55%) patients with segmental necrotising glomerulonephritis and in 8 of 18 (44%) of those with ANCA-associated systemic vasculitis without renal involvement. ANA were associated more often with pANCA and microscopic polyarteritis than with cANCA (P < 0.05). Patterns were speckled (n = 23), homogeneous (n = 10) or nucleolar (n = 4). Anticardiolipin antibodies were also common, occurring in 10 of 25 (40%) patients with Wegener's granulomatosis, in 8 of 14 (57%) patients with microscopic polyarteritis and in 6 of 18 (33%) of those with a systemic vasculitis. However, anticardiolipin antibodies did not correlate with the presence of ANCA in any of the disease groups. Anti-GBM antibodies were demonstrated in only 2 of 25 (8%) patients with Wegener's granulomatosis, in 1 patient with microscopic polyarteritis (1/14, 7%) and in 1 with segmental necrotising glomerulonephritis (1/11, 9%). All four patients with anti-GBM antibodies had either cANCA or pANCA. In the second part of the study, the target antigens of ANCA were determined in Wegener's granulomatosis, microscopic polyarteritis, systemic vasculitis, inflammatory bowel disease, rheumatoid arthritis and systemic lupus erythematosus (SLE). Of the 19 sera with cANCA, 13 (68%) were directed against proteinase 3; other antigens were myeloperoxidase (1/19, 5%), elastase and lactoferrin together (1/19, 5%), lysozyme (1/19, 5%) or unknown (3/19, 16%). Of the 12 (58%) sera from patients with Wegener's granulomatosis who had cANCA, 7 bound to proteinase 3. Antimyeloperoxidase antibodies were present in 14 of 45 (31%) sera with pANCA; other antigens were proteinase 3 (5/45, 11%), elastase (3/45, 78%), lactoferrin (1/45, 2%), cathepsin G (5/45, 11%) or unknown (17/45, 38%). Antimyeloperoxidase antibodies were common in microscopic polyarteritis (6/14, 43%) and systemic vasculitis (5/16, 31%). However, the majority of target antigens in systemic vasculitis and rheumatoid arthritis with pANCA were not determined. "Atypical" ANCA were present in four patients, one with inflammatory bowel disease (1/8, 13%) and three with SLE (3/15, 20%). The specificities were cathepsin G, cathepsin G plus lactoferrin, or unknown in two sera. A recent report has suggested that bactericidal/permeability-increasing protein may be the target in patients with inflammatory bowel disease.

Objective: To quantify the magnitude and distribution of osteoporosis in rheumatoid arthritis (RA)., Methods: Bone mineral density (BMD) was measured by dual x-ray absorptiometry, in a monozygotic co-twin control study., Results: BMD was reduced at most skeletal sites in the twin with RA compared with the co-twin (lumbar spine 4.6%, femoral neck 9.7%, total body 5.7%). Differences in lean soft tissue (5.6% for total body) correlated with differences in BMD between twins at multiple sites., Conclusion: Osteoporosis in RA is generalized and may be related to loss of mobility or muscle mass associated with the disease.

Thirty-one patients aged over 60 yrs and with lupus anticoagulant (LA) were reviewed for their drug intake. Twenty-three (73%) were taking cinchona alkaloids, 10 (32%) quinine for night cramps, 11 (35%) quinidine for cardiac arrhythmia and 2 (6%) were taking both. These frequencies of drugs usage differed significantly from age and sex matched controls (p < 0.001). Five patients had features suggestive of the antiphospholipid syndrome. Repeat testing showed persistent LA activity in all but 2 of 5 patients in whom the relevant drug had been ceased. This is the first description of a possible causal association between LA and quinine therapy.

The familial occurrence of scleroderma is uncommon particularly the limited (CREST) form. We describe 2 families in which such an association occurred. Family pedigree 1 consists of 2 of 3 sisters with CREST scleroderma. Both affected sisters shared HLA types and C4 allotypes including DR5, found more frequently in patients with scleroderma. The unaffected sister did not share this MHC allele. Family pedigree 2 includes a grandmother and grandson with CREST scleroderma as well as a family member with Raynaud's phenomena alone. We conclude that familial occurrence of scleroderma may be associated with shared class II MHC antigens.

We performed a 12-month, double-blind, randomised, placebo-controlled study to determine the long term effect of misoprostol (600-800 micrograms/d) in the prevention of gastric ulcers and gastroduodenal erosions in 83 arthritis patients on chronic NSAID therapy. Patients underwent endoscopy at 0, 3, 6 and 12 months. At the initial endoscopy, 12 patients had an ulcer (11 gastric), which was healed prior to randomization. Seventy eligible patients reached the 3 month endoscopy. Four (12.5%) of the 32 patients given misoprostol developed a gastric ulcer compared with 11 (28.9%) of the 38 on placebo (p < 0.05, life-table analysis). Six of the 11 patients with an initial gastric ulcer developed a further gastric ulcer, compared to 9 of 58 patients without an initial ulcer (p < 0.05). We conclude that misoprostol decreases the cumulative development of NSAID-induced gastric ulcers. Patients with a previous NSAID-ulcer have a higher risk of further ulceration.

The presence of antibodies to cardiolipin and the lupus anticoagulant were investigated in 189 couples with recurrent abortion. Abnormal coagulation results as measured by an elevation of the APTT or KCT were found in 6% and 7% of patients, respectively; however, the lupus anticoagulant was detected in only 3% of patients. Anticardiolipin antibody levels higher than normal were found in 15% of patients. There was no significant difference between parameters in primary as compared to secondary recurrent aborters or subfertile compared to fertile recurrent aborters. The success of the next pregnancy could not be predicted by any of the laboratory tests.

A retrospective survey of all patients with positive anti-centromere antibody (ACA) determinations over a 5-year period was undertaken. Of the 52 patients identified, seven denied symptoms of Raynaud's phenomenon, all of whom had antibody titres of 2560 or less. One of these showed a 16-fold increase in titre with the onset of Raynaud's, 12 years after original presentation. The remaining 45 patients experienced Raynaud's on cold exposure. Within this group, seven developed thrombotic vascular disease, five of whom were associated with an ACA titre of 20,480 or above. Another two with similar high ACA titres developed hyper-reninaemic hypertension, suggesting disease of the renal vasculature and associated ischaemia. Where it was possible to ascertain, seven of eight with high titre ACA developed sclerodactyly. In contrast, this was not seen in those with low titre ACA of 2560 or less and who also denied Raynaud's phenomenon.

Patients with rheumatoid arthritis (RA) and osteoarthritis (OA) were compared for the incidence of deep venous thrombosis (DVT) after total hip replacement (THR). RA patients after total knee replacement (TKR) were also compared for the incidence of DVT. The relative risk of OA patients developing DVT after THR was 2.3 times that of RA patients. In RA patients after TKR, the chance of DVT was 4.8 times greater than after THR, implying that added stress in knee surgery can overcome the inherent protection RA patients may have. Although salicylates may be protective, firm conclusions regarding the effect of drugs, including corticosteroids on the development of DVT could not be made.

Four commercially available assays were compared with a 14C DNA Farr assay for their ability to detect anti-DNA antibodies in 119 sera from 109 patients with systemic lupus erythematosus (SLE) and 25 control sera. The 14C DNA Farr assay was the most sensitive and specific assay (SLE, 57% positive, controls, 0%). A commercial 125I DNA Farr assay was significantly less sensitive (SLE, 39% positive). The fluorescence human chromosomal preparation assay was as sensitive as the 14C DNA Farr assay (SLE, 58% positive) but less specific (controls, 8% positive). The immunofluorescence Crithidia luciliae assay was specific, but less sensitive (SLE, 37% positive) than the 14C DNA Farr assay. Adaptation of Crithidia to immunoperoxidase did not alter its sensitivity or performance. These results confirm that the 14C DNA Farr assay, locally refined and performed by experienced hands, is the most sensitive and specific assay for anti-DNA antibodies. The 125I DNA Farr was no more sensitive than the Crithidia assay but considerably more laborious. The human chromosomal preparation may be suitable as a rapid screening test for anti-DNA antibodies.

A women with longstanding seropositive rheumatoid arthritis presented with the insidious onset of a hyperviscosity syndrome. This responded to plasma exchange and corticosteroids. Plasma exchange was complicated by severe bleeding which was associated with disturbances of coagulation and of platelet function related to the marked increase in plasma immunoglobulins.

Anticardiolipin antibodies (aCL) were measured in the sera of patients with different connective tissue diseases and spondyloarthropathies. Elevated antibody binding was found in systemic lupus erythematosus (SLE), rheumatoid arthritis, scleroderma, primary sicca syndrome, dermatopolymyositis and psoriatic arthritis but not in ankylosing spondylitis. The 15 highest binding SLE patients included 10 with Raynaud's phenomenon, 5 with livedo reticularis, 7 with vasculitis, 3 with major thrombotic episodes and 3 with spontaneous abortions. aCL were also measured in patients with these clinical features in isolation. Seven of 18 patients with multiple thromboses and 3/22 with multiple spontaneous abortions had raised aCL binding. Normal or near normal levels were found in patients with idiopathic thrombocytopenia, livedo reticularis, a single cerebral thrombosis and uncomplicated myocardial infarction.

Affinity purified SS-B was characterized as a protein with immunoreactive polypeptides of 40K and 29K. A modified Farr assay and an enzyme linked immunosorbent assay (ELISA) were 100- to 1,000-fold more sensitive than immunodiffusion and showed an association with the systemic manifestations of primary sicca syndrome and Sjögren's syndrome with systemic lupus erythematosus. The ELISA was sufficiently sensitive to detect class specific antibodies in saliva and lymphocyte culture supernatants.

A young woman with idiopathic temporal lobe epilepsy developed biopsy-proven oesinophilic fasciitis 16 months after the initiation of phenytoin therapy. Six months after withdrawal of this medication the fasciitis disappeared, and after 5 yr it has not recurred. This case highlights a possible association between the development of oesinophilic fasciitis and the use of medications such as phenytoin.

Lupoid thrombocytopenia is herein defined as a disorder in which patients with thrombocytopenia have a positive Hep 2 antinuclear antibody. Although these patients may have other clinical or laboratory findings consistent with systemic lupus erythematosus, they do not satisfy the revised diagnostic criteria set down by the American Rheumatism Association (1982). In all other respects they have similar findings to patients with idiopathic thrombocytopenic purpura. Six patients are described with their clinical and laboratory features. It is proposed that this disorder should be distinguished from other forms of autoimmune thrombocytopenia including that associated with systemic lupus erythematosus.

A library of monoclonal antibodies (MCA) reactive with DNA was derived from mice with lupus-like disease. The combining reactions of the antibodies was determined by ELISA, precipitation assay and indirect immunofluorescence assay on cells. On the basis of their reactions in these assays, the MCA have been classified into five taxonomic groups. MCA in Group I react with conformational determinants on double-stranded DNA (dsDNA); those in Group II with conformational backbone-dependent sugar-phosphate determinants on dsDNA and single-stranded DNA (ssDNA); those in Group III with determinants predominantly expressed on ssDNA; those in Group IV with base-dependent determinants on ssDNA, and those in Group V with determinants on both DNA and RNA. It is concluded that antibodies which react with DNA are collectively of limited heterogeneity with regard to their specificity. The study illustrates how, upon traditional interpretation, different assay systems may give discordant results in the assignment of specificity to antibodies reactive with DNA.

Nuclear ribonuclear protein (nRNP) and Sm were extracted from a 30-60% ammonium sulphate fraction of rabbit thymus extract by affinity chromatography. Immunoadsorbent columns were prepared from IgG extracted from an anti-nRNP serum, an anti-Sm serum and two monoclonal autoantibodies derived from a MRL/lpr mouse. All four immunoadsorbents isolated both nRNP and Sm antigens indicating that they exist as the 'nRNP/Sm complex' A species of Sm which did not bind to the anti-nRNP column and which was subsequently purified with the anti-Sm column was termed 'free Sm'. The Sm in the complex and free Sm were immunologically identical on immunodiffusion and gave similar polypeptide bands on polyacrylamide gel electrophoresis. However, they differed in that complexed Sm was sensitive to heat and RNAase. These studies provide direct evidence of a physical association between the nRNP and Sm antigens and indicate an additional molecular species of Sm whose resistance to RNAase may be due to different associated RNA species.