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Query: UMLS:C0409974 (lupus)
 22,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Particular susceptibility to systemic lupus erythematosis (SLE) could be due to a certain alleles of class I, II or III of the major histocompatibility complex (MHC). The existence of total hereditary deficiencies of factor 2 or 4 of the complement in this syndrome suggests the presence of silent alleles which could conceivably play a determining role in the appearance of SLE. In this study, the HLA haplotypes and complotypes (C2, C4, Bf) were determined in 20 individuals suffering from SLE, and compared with 108 healthy, genotyped individuals. The results obtained showed a significant increase in the frequency of C4 BQ0 in patients compared with that found in controls (chi 2 = 12.27, p less than 0.001, Relative Risk = 3.78), and confirm the HLA association, DR3/SLE (chi 2 = 5.45, p less than 0.02, RR = 2.53).
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PMID:[Familial studies of systemic lupus erythematosus. HLA markers and complotypes]. 353 94

We have studied a family in which the proband had systemic lupus erythematosus and selective incomplete deficiency of the fourth component of complement (C4) (2-5% of the normal level). An additional six healthy family members also had low C4 levels (2.4-24.1% of normal) but no evidence of lupus. This form of inherited C4 deficiency differs from that in previously reported families in that inheritance was autosomal dominant (rather than recessive), C4 levels were markedly reduced (but not undetectable), and there was no linkage to HLA, BF, or C4 structural loci, all known to be within the major histocompatibility complex.
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PMID:Inherited incomplete deficiency of the fourth component of complement (C4) determined by a gene not linked to human histocompatibility leukocyte antigens. 648 Aug 34

Immunogenetic factors are important in systemic lupus erythematosus (SLE) and deficiency of a number of complement components is often associated with a lupus-like illness. The complement components Bf, C2 and C4 are encoded within the human major histocompatibility complex (MHC) and are polymorphic. A study of HLA and Bf and C4 polymorphism in 43 patients with SLE was undertaken firstly, to determine whether partial deficiency of C2 and C4 may predispose to disease and secondly, because it may allow the better definition of important supratypes associated with the disease and which may include the relevant disease gene(s). An increased frequency of C4A null alleles has been shown in SLE, with a minimal estimated C4A null gene frequency of 0.32 versus 0.20, but no case of partial C2 deficiency was identified. These results may indicate a direct role for partial C4 deficiency or that C4A null may be a marker for an important supratype which includes the relevant disease gene(s).
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PMID:Complement allotyping in SLE: association with C4A null. 660 18

A young girl presenting with recurrent pulmonary infections and atypical lupus erythematosus was totally deficient in C4. In one sister, also deficient in C4, the same symptoms developed. Results of family studies were consistent with an autosomal recessive mode of transmission and with linkage of the genes determining C4 deficiency to those of the major histocompatibility complex. The patient's serum and red cells were Chido- and Rodgers-negative. Humoral and cellular immunity were normal, except for a low lymphocyte response in mixed lymphocyte culture. The cellular function of the patient's polymorphonuclear leukocytes was normal, for both phagocytosis and bactericidal activity using Candida albicans. However, in the presence of C4-deficient serum, opsonin generation and bactericidal indexes were diminished. These defects were completely reversible upon addition of purified C4.
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PMID:Genetic deficiency of C4 presenting with recurrent infections and a SLE-like disease. Genetic and immunologic studies. 688 Nov 82

We have investigated the phenotypic and functional characteristics of murine pre-B cells obtained in semisolid and liquid culture with stem cell factor (SCF) and interleukin 7 (IL-7). Both serum-supplemented and serum-deprived culture conditions were used. The source of bone marrow cells was either normal mice (CD1 and C3H) or the lupus strain of mice MRL/lpr and its congenic strain MRL/+. SCF (100 ng/ml) and IL-7 (250 ng/ml) supported murine B cell proliferation in vitro from all the murine strains analyzed both in serum-supplemented and serum-deprived conditions. Maximal colony growth was observed in both cases when the factors were used in combination. The growth factors alone induced some colony growth in serum-supplemented cultures but were either ineffective or had modest activity in serum-deprived cultures. Cells harvested from the colonies or generated in liquid cultures and stimulated with SCF + IL-7 in the absence of serum had almost exclusively a pre-B cell phenotype (BP-1+, B220+, slg-, CD4-, CD8-, Mac-1-, RB-6-). Both the maximal colony growth in semisolid culture and the maximal number of cells in liquid culture were observed at day 12-14. At this time, the pre-B cells failed to differentiate further and started to die. Pre-B cells generated in vitro were, however, capable of differentiating in vivo. SCID mice injected with 2 x 10(6) pre-B cells had readily detectable serum levels of IgM (54 +/- 26 micrograms/ml) and IgG (60 +/- 95 micrograms/ml) at 4 weeks and 6 weeks posttransplantation, respectively. Mature B and T cells of the donor major histocompatibility complex type were detected in the SCID mice at sacrifice 14 weeks posttransplantation. These data indicate that purified (> 80% BP-1+) populations of functional pre-B cells can be grown from murine bone marrow of normal mice as well as of lupus mice in serum-deprived cultures stimulated with SCF and IL-7. These cultures, therefore, provide a highly enriched source of pre-B cells but also contain T cell precursors that differentiate upon adoptive transfer into SCID mice.
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PMID:Functional characterization of lymphoid cells generated in serum-deprived culture stimulated with stem cell factor and interleukin 7 from normal and autoimmune mice. 754 56

An immunohistochemical analysis of skin biopsies was performed in 18 patients with cutaneous lupus erythematosus (LE), using the alkaline phosphatase and monoclonal anti-alkaline phosphatase method (APAAP). The study group was subdivided on the basis of clinical criteria into 10 patients with chronic discoid LE (CDLE) and eight patients with subacute cutaneous LE (SCLE). Using a panel of monoclonal antibodies the following results were obtained: (i) ICAM-1 was expressed on epidermal keratinocytes, dermal inflammatory cells, and endothelial cells in most biopsies, whereas LFA-1 was confined to the dermis. Attachments between keratinocytes or endothelial cells and activated T lymphocytes via ICAM-1/LFA-1 may be a possible mechanism of target/effector recognition in cutaneous LE. (ii) HLA-DR was expressed on epidermal keratinocytes and cells of the dermal infiltrate, but not on endothelial cells. HLA-DR+ cells probably function as antigen-presenting cells, leading to major histocompatibility complex-restricted cellular cytotoxicity in cutaneous LE. (iii) Interleukin 2 receptor expression on dermal inflammatory cells was weak, indicating non-specific activation of T lymphocytes. (iv) The dermal inflammatory cells were T lymphocytes, mainly of the helper/inducer subtype. B lymphocytes were rarely found in the dermis. In general, no significant immunohistochemical differences were found between CDLE and SCLE, suggesting that these variants represent clinical subtypes rather than different pathogenetic entities.
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PMID:Immunohistochemical analysis of chronic discoid and subacute cutaneous lupus erythematosus--relation to immunopathological mechanisms. 775 49

Recent studies have suggested an association between primary antiphospholipid syndrome (PAPS), antiphospholipid antibodies and some major histocompatibility complex (MHC) antigens. We have studied the relationship between MHC class II antigens and PAPS in 19 patients from the south of Spain. Univariant analysis showed an association between PAPS and HLA-DQ7 (47% vs 25%l P = 0.3), DR4 (32% vs 16%; P = 0.08) and DQ3 (63% vs 39%; P = 0.04). However, multivariant analysis confirmed the association with DQ7 (RR = 2.5; CI 80%: 1.3-4.7) and DR4 (RR = 2.2; CI 80%: 1.1-4.4) but not with DQ3. When we introduced DRw53 into this analysis, we noticed a DR4 confounding effect, with DQ7 (RR = 3.1; CI 80%: 1.7-5.8) and Drw53 (RR = 2.3; CI 80%: 1.2-4.4) remaining as the most important HLA antigens related to PAPS. In conclusion, in PAPS patients from the South of Spain, HLA-DQ7 antigen showed the highest relative risk for PAPS, followed by DRw53.
Lupus 1995 Feb
PMID:Association between HLA class II antigens and primary antiphospholipid syndrome from the south of Spain. 776 40

Patients with systemic lupus erythematosis (SLE) often manifest features of other autoimmune diseases. In this review, we provide a detailed compendium of features of SLE that overlap with other conditions. This compendium is important because a critical feature in our understanding of autoimmunity has been the clustering of coexisting/different autoimmune diseases both within an affected patient and within a pedigree. Indeed, autoimmune disorders share a variety of similar clinical and serological defects. For example, all autoimmune disorders are associated with the elaboration of autoantibodies and/or the production of self-reactive mononuclear cell populations; many have high levels of immune complexes and defects in cell-mediated immunity. Several diseases share similar genetic backgrounds, as reflected by study of loci within the major histocompatibility complex. In part the coassociation is due to common genetic tendencies with different environmental precipitating agents (trigger mechanisms). It is likely that many factors can modulate the immune system to autoimmunity in the presence of an appropriate genetic background, eg, drugs, viral infections, UV irradiation, and toxins, ie, toxic oil syndrome and L-tryptophan-induced eosinophilic myalgia. The coexistence of SLE with other autoimmune diseases is an excellent venue to understand these events, and we believe that the presence of other autoimmune diseases in patients with SLE can be called the kaleidoscope of autoimmunity.
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PMID:The coexistence of systemic lupus erythematosus with other autoimmune diseases: the kaleidoscope of autoimmunity. 783 52

MRL-lpr mice develop aggressive autoimmune kidney disease associated with increased or de novo renal expression of major histocompatibility complex (MHC) class II molecules and a massive systemic expansion of CD4-CD- double negative (DN) T cells. Whereas non-MHC linked genes can have a profound effect on the development of nephritis, lymphadenopathy, and anti-DNA antibody production in MRL-lpr mice, the role of MHC molecules has not been unequivocally established. To study the role of MHC class II in this murine model of systemic lupus erythematosis, class II-deficient MRL-lpr mice (MRL-lpr -/-) were created. MRL-lpr -/- mice developed lymphadenopathy but not autoimmune renal disease or autoantibodies. This study demonstrates that class II expression is critical for the development of autoaggressive CD4+ T cells involved in autoimmune nephritis and clearly dissociates DN T cell expansion from autoimmune disease initiation.
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PMID:Prevention of nephritis in major histocompatibility complex class II-deficient MRL-lpr mice. 790 20

Mice injected at birth with semi-allogeneic lymphoid cells develop a lupus-like autoimmune syndrome in which donor B cells are polyclonally activated by host alloreactive CD4+ T cells, producing autoantibodies and immune complex-mediated glomerulonephritis. It has been demonstrated that the recognition of major histocompatibility complex (MHC) class II alloantigens triggers the development of a complete disease. But differences in either MHC class I molecules or Mls-1 antigens are not sufficient to induce production of autoantibodies. Here we have investigated whether differences in other non-MHC alloantigens could induce a similar autoimmune disease and whether the maternal environment could modulate the T-B allogeneic co-operation in this model. For this purpose (BALB/c x BC20)F1 hybrid females were backcrossed with BC20 males. R2 mice obtained in this backcross were neonatally injected with 10(8) (C57BL/6 x BALB.Igb)F1 spleen cells and the tolerance against maternal derived BALB/c alloantigens as well as the development of autoimmune manifestations were subsequently evaluated. In contrast to R2 mice injected at birth with (C57BL/6 x BALB.Igb)F1 cells, control R2 mice rejected skin grafts from BALB/c mice and B cells from (C57BL/6 x BALB.Igb)F1 mice, independently of their H-2 haplotype (H-2b/d or H-2b/b). Nevertheless, after neonatal injection of (C57BL/6 x BALB.Igb)F1 cells, none of 19 H-2b/d R2 injected mice presented autoimmune manifestations, in contrast with the typical autoimmune disease observed in all neonatally injected H-2b/b R2 mice (26 mice). These results support that the development of autoimmunity in this model depends exclusively upon differences in MHC class II alloantigens and that the relationship between mother and fetus, through the pregnancy or the breast suckling, is not sufficient to inhibit cytolytic and allo-helper responses against non-inherited maternal-derived alloantigens.
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PMID:Differences in non-MHC alloantigens promote tissue rejection but fail to mediate allogeneic co-operation and autoimmunity in mice neonatally injected with semi-allogeneic F1 B cells. 792


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