The revised criteria for the classification of rheumatoid arthritis (RA) were formulated from a computerized analysis of 262 contemporary, consecutively studied patients with RA and 262 control subjects with rheumatic diseases other than RA (non-RA). The new criteria are as follows: 1) morning stiffness in and around joints lasting at least 1 hour before maximal improvement; 2) soft tissue swelling (arthritis) of 3 or more joint areas observed by a physician; 3) swelling (arthritis) of the proximal interphalangeal, metacarpophalangeal, or wrist joints; 4) symmetric swelling (arthritis); 5) rheumatoid nodules; 6) the presence of rheumatoid factor; and 7) radiographic erosions and/or periarticular osteopenia in hand and/or wrist joints. Criteria 1 through 4 must have been present for at least 6 weeks. Rheumatoid arthritis is defined by the presence of 4 or more criteria, and no further qualifications (classic, definite, or probable) or list of exclusions are required. In addition, a "classification tree" schema is presented which performs equally as well as the traditional (4 of 7) format. The new criteria demonstrated 91-94% sensitivity and 89% specificity for RA when compared with non-RA rheumatic disease control subjects.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/art.1780310302

The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis.

Statistical method for testing the neutral mutation hypothesis by DNA polymorphism.

Systemic lupus erythematosus (SLE) is a clinically heterogeneous disease, which is autoimmune in origin and is characterized by the presence of autoantibodies directed against nuclear antigens. It is a multi-system disease, and patients can present in vastly different ways. Prevalence varies with ethnicity, but is estimated to be about 1 per 1000 overall with a female to male ratio of 10:1. The clinical heterogeneity of this disease mirrors its complex aetiopathogenesis, which highlights the importance of genetic factors and individual susceptibility to environmental factors. SLE can affect every organ in the body. The most common manifestations include rash, arthritis and fatigue. At the more severe end of the spectrum, SLE can cause nephritis, neurological problems, anaemia and thrombocytopaenia. Over 90% of patients with SLE have positive anti-nuclear antibodies (ANA). Significant titres are accepted to be of 1:80 or greater. SLE is a relapsing and remitting disease, and treatment aims are threefold: managing acute periods of potentially life-threatening ill health, minimizing the risk of flares during periods of relative stability, and controlling the less life-threatening, but often incapacitating day to day symptoms. Hydroxychloroquine and non-steroidal anti-inflammatory drugs are used for milder disease; corticosteroids and immunosuppressive therapies are generally reserved for major organ involvement; anti-CD20 monoclonal antibody is now used in patients with severe disease who has not responded to conventional treatments. Despite enormous improvements in prognosis since the introduction of corticosteroids and immunosuppressive drugs, SLE continues to have a significant impact on the mortality and morbidity of those affected.

/pdf/systemic-lupus-erythematosus-34b38trluu.pdf

Systemic lupus erythematosus

In sharp distinction to organ-specific autoimmune diseases such as thyroiditis, diabetes, or myasthenia gravis, systemic lupus erythematosus (SLE) is a constellation of signs and symptoms classified as one nosologic entity. Indeed, it is the diversity of presentation, accumulation of manifestations over time, and undulating disease course that challenge the most astute of clinicians. With rare exception, the unifying laboratory abnormality is the presence of circulating antinuclear antibodies (ANA). Acknowledging the complexity of this disease, its broad differential diagnosis, and the need to develop better and more specific therapies, the American College of Rheumatology (ACR) has designated 11 diagnostic criteria (presented in Table 15A-1) (1,2). These criteria reflect the major clinical features of the disease (mucocutaneous, articular, serosal, renal, neurologic) and incorporate the associated laboratory findings (hematologic and immunologic). The presence of four or more criteria is required for diagnosis. They need not necessarily present simultaneously: a single criterion such as arthritis or thrombocytopenia may recur over months or years before the diagnosis can be confirmed by the appearance of additional features. While there is incomplete agreement among rheumatologists as to whether these criteria need to be strictly applied in a practice setting, or reserved only for formal academic studies, they do facilitate a methodologic approach to evaluate a patient.

/pdf/systemic-lupus-erythematosus-1yp4wnywfd.pdf

Systemic Lupus Erythematosus

Rheumatoid arthritis is the most common inflammatory arthritis and is a major cause of disability. It existed in early Native American populations several thousand years ago but might not have appeared in Europe until the 17th century. Early theories on the pathogenesis of rheumatoid arthritis focused on autoantibodies and immune complexes. T-cell-mediated antigen-specific responses, T-cell-independent cytokine networks, and aggressive tumour-like behaviour of rheumatoid synovium have also been implicated. More recently, the contribution of autoantibodies has returned to the forefront. Based on the pathogenic mechanisms, specific therapeutic interventions can be designed to suppress synovial inflammation and joint destruction in rheumatoid arthritis.

/pdf/evolving-concepts-of-rheumatoid-arthritis-1bu40832qh.pdf

Evolving concepts of rheumatoid arthritis

Previous testing of patients with rheumatoid arthritis showed that one HLA-D type, Dw4, occurred more frequently than in normal controls. B-cell alloantigens closely related to HLA-D can now be identified by a simple serologic procedure. Using this test, I studied 80 white patients with erosive, rheumatoid-factor-positive rheumatoid arthritis. The B-cell alloantigen HLA-DRw4 occurred in 70 per cent of 54 patients, as compared to 28 per cent of the 68 normal controls (P less than 10(-5)). Both groups were also tested for the HLA-A, B and C antigens and for HLA-D. HLA-Dw4 occurred in 54 per cent of the patients and 16 per cent of the controls (P less than 10(-5)). Small differences observed in several of the HLA-A and B antigens were not statistically significant. The results indicate that rheumatoid arthritis in whites is associated with genes of the HLA-D region and that immunogenetic factors linked to HLA have a role in its pathogenesis.

https://www.nejm.org/doi/pdf/10.1056/NEJM197804202981602?listPDF=true

Association of the B-Cell Alloantigen DRw4 with Rheumatoid Arthritis

We studied the autoimmune serologic features and histocompatibility antigen associations of 27 patients who had a widespread, nonscarring and often photosensitive form of histologically specific cutaneous lupus erythematosus. We designated this disorder as subacute cutaneous lupus erythematosus. Skin lesions from this disorder can be distinguished from scarring discoid lupus erythematosus lesions both on a morphologic and histopathologic basis. Antinuclear and anticytoplasmic antibodies (Ro or Ro and La) and circulating immune complexes were frequently present in patients with subacute cutaneous lupus erythematosus, whereas rheumatoid factor and anti-lymphocyte, anti-DNA, anti-nRNP, and anti-Sm antibodies were found less frequently. Patients having annular skin lesions represented a particularly homogeneous subgroup in which there was a striking concordance of anti-Ro antibodies and the HLA-DR3 phenotype. These studies clearly establish that the presence of these lesions can serve as a cutaneous marker for a distinct subset of patients with lupus erythematosus who share similar clinical, serologic, and genetic features.

Serologic and HLA Associations in Subacute Cutaneous Lupus Erythematosus, a Clinical Subset of Lupus Erythematosus

Glomerulonephritis with deposition of Australia antigen-antibody complexes in glomerular basement membrane.

Background Good HLA-A, HLA-B, and HLA-DR matches do not guarantee rejection-free renal transplantation. Some kidney transplants fail despite such matches, suggesting that other antigens might be targets for rejection. Major-histocompatibility-complex (MHC) class I–related chain A (MICA) antigens are polymorphic and can elicit antibody production. We sought to determine whether an immune response to MICA antigens might play a role in the failure of kidney allografts. Methods Pretransplantation serum samples from 1910 recipients of kidney transplants from deceased donors were tested for anti-MICA antibodies with an assay in which single MICA antigens were attached to polystyrene microspheres. Results Antibodies against MICA alleles were detected in 217 of the 1910 patients (11.4%). The presence of MICA antibodies was associated with renal-allograft rejection. The mean (±SE) 1-year graft-survival rate was 88.3±2.2% among recipients with anti-MICA antibodies as compared with 93.0±0.6% among recipients without...

https://www.nejm.org/doi/pdf/10.1056/NEJMoa067160

Antibodies against MICA Antigens and Kidney-Transplant Rejection

A gene involved in psoriasis susceptibility was localized to the distal region of human chromosome 17q as a result of a genome-wide linkage analysis with polymorphic microsatellites and eight multiply affected psoriasis kindreds. In the family which showed the strongest evidence for linkage, the recombination fraction between a psoriasis susceptibility locus and D17S784 was 0.04 with a maximum two-point lod score of 5.33. There was also evidence for genetic heterogeneity and although none of the linked families showed any association with HLA-Cw6, two unlinked families showed weak levels of association. This study demonstrates that in some families, psoriasis susceptibility is due to variation at a single major genetic locus other than the human lymphocyte antigen locus.

https://science.sciencemag.org/content/sci/264/5162/1141.full.pdf

Peter Stastny

Papers

Association of the B-Cell Alloantigen DRw4 with Rheumatoid Arthritis

Serologic and HLA Associations in Subacute Cutaneous Lupus Erythematosus, a Clinical Subset of Lupus Erythematosus

Glomerulonephritis with deposition of Australia antigen-antibody complexes in glomerular basement membrane.

Antibodies against MICA Antigens and Kidney-Transplant Rejection

Gene for familial psoriasis susceptibility mapped to the distal end of human chromosome 17q