The 1971 preliminary criteria for the classification of systemic lupus erythematosus (SLE) were revised and updated to incorporate new immunologic knowledge and improve disease classification. The 1982 revised criteria include fluorescence antinuclear antibody and antibody to native DNA and Sm antigen. Some criteria involving the same organ systems were aggregated into single criteria. Raynaud's phenomenon and alopecia were not included in the 1982 revised criteria because of low sensitivity and specificity. The new criteria were 96% sensitive and 96% specific when tested with SLE and control patient data gathered from 18 participating clinics. When compared with the 1971 criteria, the 1982 revised criteria showed gains in sensitivity and specificity.In 1971 a subcommittee of the American Rheumatism Association (ARA) published a report on "The From the Subcommittee for Systemic Lupus Erythematosus Criteria of the American Rheumatism Association Diagnostic and Therapeutic Criteria Committee.Developed with the assistance of Donald Young. Eng M. Tan, MD: Chairman of Subcommittee for Systemic

Understanding the inheritance of rheumatoid arthritis (RA) has been the quest of intense investigation over the last decade. One major focus of these efforts has been the attempt to identify genes within the class I1 region of the major histocompatibility complex (MHC) that confer susceptibility for disease. These studies have been based largely on finding associations between class I1 serologic specificities and disease. The results have not been simple to interpret, and lucid analysis is made more difficult by the highly complicated nomenclature that is used to describe the class I1 HLA system. The advent of recombinant DNA technology, however, has greatly expanded our knowledge of this system over the last few years and has offered alternative interpretations of disease association data. One such interpretation, the shared epitope hypothesis, has been described previously (1) and is the subject of this review.To understand the shared epitope hypothesis, one must have some knowledge of the genetic organization of the class I1 region and of the biochemical structure of class I1 molecules. Briefly, the human class I1 region (Figure 1) extends to nearly l , OOO, OOO base pairs, and includes at least 14 different genes. With the exception of DOp and DZa, these genes are generally found in 1 of 3 major subregions: DR, DQ, or DP.Each subregion contains at least 1 functional a Figure 2. Alpha and beta chains from the DQ subregion are polymorphic (i.e., there are multiple alleles at each locus in the population), and together they encode the DQ serologic specificities (DQwl-3).The DR subregion also contains 2 functional p chain genes, designated DRPI and DRPIII. These p chains are both polymorphic. The D W I gene encodes the classic DR specificities (DR1-14); the DRPIII gene encodes the DRw52 and DRw53 specificities. The genes within the DR and DQ subregions are very closely linked and are almost always inherited together as a unit. Therefore, DR and DQ subregion alleles form stable haplotypes in the population. For example, the DR4 allele (encoded by the D W I gene) is almost always found in association with DRw53 (encoded by DRpIII) and DQw3 (encoded by DQ a and P), thus forming the typical DR4,DRw53,DQw3 haplotype. As discussed herein, all the variability between different DR4 haplotypes is located in the DRPI gene. The other linked genes, namely DRPIII, DQa, and DQP, are identical in all DR4 haplotypes, with few exceptions (2,3).The structural features of class I1 molecules at the cell surface are shown in Figure 2 (top). For comparison, class I molecules are also shown. In the case of class I1 molecules, both a and P chain molecules are inserted into the membrane and associate with each other in a noncovalent fashion to form an alp heterodimer. The class I1 p chain contains 2 immunoglobulin-like external domains. The first, or N-terminal, domain (Figure 2) is the site of most of thevariability

Celiac disease is an intestinal inflammatory disorder induced by dietary gluten in genetically susceptible individuals. The mechanisms underlying the massive expansion of interferon γ–producing intraepithelial cytotoxic T lymphocytes (CTLs) and the destruction of the epithelial cells lining the small intestine of celiac patients have remained elusive. We report massive oligoclonal expansions of intraepithelial CTLs that exhibit a profound genetic reprogramming of natural killer (NK) functions. These CTLs aberrantly expressed cytolytic NK lineage receptors, such as NKG2C, NKp44, and NKp46, which associate with adaptor molecules bearing immunoreceptor tyrosine-based activation motifs and induce ZAP-70 phosphorylation, cytokine secretion, and proliferation independently of T cell receptor signaling. This NK transformation of CTLs may underlie both the self-perpetuating, gluten-independent tissue damage and the uncontrolled CTL expansion leading to malignant lymphomas in severe forms of celiac disease. Because similar changes were detected in a subset of CTLs from cytomegalovirus-seropositive patients, we suggest that a stepwise transformation of CTLs into NK-like cells may underlie immunopathology in various chronic infectious and inflammatory diseases.

These findings suggest that the psoriasis phenotype results from two patterns of MHC effect. The first involves the classic psoriasis susceptibility gene C*06, which confers more penetrant skin disease with less prevalent and more time-dependent musculoskeletal phenotype development. The second pattern appears to be mediated by HLA-B alleles, notably B*27, and includes temporally more coincident musculoskeletal involvement that is nearly equivalent in penetrance to that of the skin disease.