Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The hypothesis that complement is important in the host response to human immunodeficiency virus (HIV) was tested. Complement C4 and Bf allotypes were determined in 26 patients who fulfilled the diagnostic criteria for persistent generalised lymphadenopathy due to HIV, 72 homosexuals who were negative for antibody to HIV, and 185 control subjects drawn from the local population. HLA-A, B, and DR were also typed and the phenotypes examined for the presence of supratypes and C4BQ0. Eleven patients (42%) had C4B null alleles compared with only 13 (18%) homosexuals who were negative for antibody and 28 (15%) controls. From estimates of gene frequencies the difference between the patients with lymphadenopathy and the controls was significant after conservative correction. In the patients only a minority (six) of the C4B null alleles were contained within ancestral haplotypes. Together with the fact that C4 null alleles result in partial deficiency of C4, this finding suggests that products of complement genes are important in infection with HIV or its consequences, or both. A role is proposed for complement and Fc receptors.
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PMID:Influence of C4 null genes on infection with human immunodeficiency virus. 313 45

Two T-lymphocyte subsets develop in the thymus which differ in the expression of glycoproteins on their cell surface. About 60% of the circulating T cells express the glycoprotein T4, while about 30% have the glycoprotein T8. T4 and T8 cells can be determined in the peripheral blood or various organs with monoclonal antibodies. T4 and T8 cells differ in their antigen recognition, have different functions, and can cause various pathohistological changes. T4 cells recognize the antigen in association with the HLA-D/DR/DP determinants. Upon antigenic stimulation they liberate various factors and initiate and amplify an immune response (T4 = helper/inducer T-cells). They can also be cytotoxic and are mediating effector functions via macrophage activation. T8 cells recognize the antigen in association with HLA-A/B/C determinants. They exert their cytotoxic or suppressive effector functions mainly in viral infections. The T4 or T8 cell-mediated pathohistological changes are discussed in the light of the well studied T-cell infiltrations in lepra lepromatosa or lepra tuberculosa. The T4/T8 cell dyscrasia in the peripheral blood, described in a variety of infectious, autoimmune or immunodeficiency diseases, may be due to enhanced proliferation, selective sequestration, reduced production or the elimination of a subset. T-cell subset analysis in joints, bronchial lavages and tissues has clarified the pathomechanism in a variety of autoimmune diseases, although the etiology remains obscure. For example, in rheumatoid arthritis, multiple sclerosis, and sarcoidosis, a T4 cell-mediated reaction with macrophage activation can be found. T4/T8 cell analysis may also be of value in dissecting heterogenous diseases, e.g. systemic lupus erythematosus. Of value is also the additional demonstration of membrane components reflecting T-cell activation (IL-2 receptor or DR-antigen expression) which serves to identify the activated T-cell subset in peripheral blood. Finally, T4/T8 cell analysis can be helpful in deciding treatment, as the T-cell subsets have a different sensitivity to immunosuppressive drugs.
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PMID:[Analysis of T-cell subpopulations. Pathophysiological concept and significance for clinical medicine]. 315 84

HLA-A, -B, -C, -DR, and -DQ antigen phenotypes were determined in 266 Caucasian homosexual men, 90 of whom were HIV-1 seronegative, 94 HIV-1 seropositive AIDS-free, and 82 with a diagnosis of AIDS [36 with Kaposi's sarcoma (KS), 34 with opportunistic infection (OI), and 12 with KS and OI]. No significant differences in HLA-A or -B antigen frequencies were found in any comparisons of these groups. However, in comparisons of seropositive AIDS-free men with the AIDS groups, HLA-Cw7 was increased in frequency in OI and HLA-DR1, -DRw14, and -DQw1 in KS. HLA-DR3 and -DQw3 frequencies were decreased in KS, and DRw53 was decreased in OI. In a cohort of 102 HIV seropositive individuals that were followed for a mean of 43 months, AIDS developed in HLA-DR1 positive men more frequently than in individuals with other HLA-DR phenotypes (p = 0.02). These results demonstrate probable genetic differences between individuals developing KS and OI and indicate that the HLA-DR1 phenotype is a risk factor in disease progression in human immunodeficiency virus (HIV)-infected individuals.
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PMID:HLA antigen frequencies in HIV-1 seropositive disease-free individuals and patients with AIDS. 321 93

Phenotypic and functional analysis of B lymphocytes in two siblings with combined immunodeficiency associated with defective expression of class I and class II major histocompatibility complex (MHC) antigens on mononuclear cells is described. The results of the analysis of the membrane phenotype of the B cells performed at the age of 1 and 5 years, respectively, by the use of monoclonal antibodies against class I (HLA-A, -B, -C) and class II (HLA-DR, -DP, -DQ) MHC antigens showed a decreased expression of class I antigens and a complete lack of class II antigens. Class I antigen expression consistently remained of the same magnitude during follow-up. Class II antigen expression remarkably had been positive early in life on B cells and activated T cells, whereas monocytes were negative for class II from birth onward. B lymphocytes of both patients responded in vitro to polyclonal activation with Staphylococcus aureus Cowan I staphylococci (SAC) with the production of IgM-type immunoglobulins only. This neonatal type of response was in agreement with the membrane immunoglobulin phenotype of the B cells since a high sIgM/sIgD ratio characteristic of neonatal B cells was present. However, the expression of the FMC7 antigen on B cells of both patients was comparable to that on B cells of normal adults. We hypothesized that the lack of MHC antigen expression may impose a resting state on the lymphocytes in these patients due to ineffective cellular interactions. In this view the high sIgM/sIgD ratio reflects the activation state of the B cells rather than the maturational state of the cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Phenotypical and functional analysis of B lymphocytes of two siblings with combined immunodeficiency and defective expression of major histocompatibility complex (MHC) class II antigens on mononuclear cells. 349 42

A 3-year-old girl developed a disseminated Mycobacterium avium infection despite treatment with eight antimycobacterial drugs. She had no pre-existent general humoral or cellular immunodeficiency. In the course of the disease B lymphocyte areas in the lymphoid tissues were replaced by histiocytes and an IgM and IgA deficiency evolved. The patient still made antibodies to concomitant micro-organisms and to transfused blood cells. Peripheral blood mononuclear cells (PBMC) had normal responses to mitogens and various antigens in vitro. However, she lacked any response to mycobacterial antigens, in vivo and in vitro. The defect appeared not to be dependent on immunosuppression by lymphocytes or monocytes or on deficient antigen presentation by monocytes. because a genetic origin could not be substantiated, acquired immunological paralysis for mycobacterial antigens was the most likely explanation. Addition of irradiated PBMC from her HLA-A, -B, -C and -DR phenotypically identical father, transferred a response to mycobacterial antigens of the patient's PBMC in vitro. We concluded that the disseminated M. avium infection was accompanied by a selective deficiency of the lymphocyte response to mycobacterial antigens which could be restored by allogeneic antigen responsive lymphocytes.
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PMID:Deficiency of immunity to Mycobacterium avium that can be restored by allogeneic lymphocytes. 365 15

Thymic biopsies from two patients with combined immunodeficiency and defective expression of HLA class I and class II antigens on blood mononuclear cells ("bare lymphocyte" syndrome) were investigated. This made possible an evaluation of the significance of HLA antigen expression in a detailed (immuno)histologic study. Both thymuses showed a normal lobular architecture with distinct cortex-medulla areas, well-differentiated epithelium, including ultrastructurally defined subtypes, and Hassall's corpuscles. Normal numbers of lymphoid cells were present and normal T-cell phenotype was found. Using anti-HLA-A,B,C antisera, confluent staining of the medulla (stroma and lymphocytes) was observed. One of the thymuses was found to be negative for HLA class II antigen expression: the other revealed only HLA-DR positivity of nonlymphoid cells in the medulla. These cells were not of epithelial nature as judged from double staining with anti-keratin antibody. There was no expression of HLA-DC/DS. These observations differ from findings in the normal thymus, wherein epithelial cells in the cortex carry HLA class I and class II antigens, and epithelial cells in the medulla express HLA class I, and for a minor part class II antigens. The results indicate a normal sequential acquisition of T-cell differentiation antigens in the thymus of both cases. It is suggested that the expression of HLA class I and class II antigens on epithelial cells in the normal thymus cortex does not play a significant role in the sequential acquisition of differentiation antigens on T lymphocytes.
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PMID:The thymus in "bare lymphocyte" syndrome: significance of expression of major histocompatibility complex antigens on thymic epithelial cells in intrathymic T-cell maturation. 387 94

A case of the bare lymphocyte without apparent immunodeficiency was observed in a 33-year-old woman who had no history of severe infections but suffered from sino-bronchial disease. No HLA-A and -B antigens (class I antigens) were detected at the cell surface of lymphocytes, granulocytes, and platelets, but they were expressed, although at a reduced level, on the cultured B lymphoid cell line. T lymphocytes were normal in number and in the relative proportion of T4/T8 and responded to mitogens but not to PPD and candida. HLA-DR antigens (class II antigens) were present on B lymphocytes and showed intermediate MLR-stimulatory capacity, which made it possible to deduce the patient's HLA genotype. She was found to be homozygous at consanguinity for HLA-A, -B, and -DR antigens. The numbers of B lymphocytes, immunoglobulins, and complements were all in the normal range; there was, however, a low level of IgM. Two-dimensional gel analysis of class I antigens revealed the presence of normally expressed beta-2 microglobulins (B2M) and an apparently single set of class I heavy chains, allowing us to consider two alternative cellular mechanisms in this defect; the presence of one abnormal class I structural gene and the regulatory mechanism that acted in cis were suggested.
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PMID:Defective expression of HLA class I antigens: a case of the bare lymphocyte without immunodeficiency. 389 4

Since interferon is known to enhance HLA A-B expression on lymphocytes from normal donors, we have tested the hypothesis that interferon could reverse the defective membrane expression of HLA antigens observed in some patients with combined immunodeficiency. Leucocytes from four patients with this syndrome, after overnight incubation with preparations of interferon, showed a clear enhancement in the percentage of cells bearing HLA A-B-C and beta 2 microglobulin (but not HLA-DR) antigens as detected by membrane immunofluorescence. Functional HLA-A and B antigens also appeared on patients' T cell blasts treated with interferon, as shown by the ability of these blasts to be destroyed by specific cytotoxic T lymphocytes. Both alpha and beta human interferons were effective. These effects were shown to be mediated by interferon (but not contaminants in our preparations) by the use of specific antiserum to interferon. It is likely that interferon acts on HLA synthesis, since in vitro addition of drugs known to inhibit nucleic acid or protein synthesis completely abolished the enhancing effect of interferon on membrane HLA expression. Interferons can therefore modulate leucocyte HLA expression and synthesis in patients with defective expression of these antigens, a finding which suggests that interferon treatment might be beneficial in this condition.
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PMID:Enhancement by interferon of membrane HLA antigens in patients with combined immunodeficiency with defective HLA expression. 619 May 92

Within the last 7 years, HLA and disease studies have made it clear that most of the diseases previously known to be HLA-A- or B-associated do in fact show stronger associations with HLA-D/DR antigens. This observation strengthens the assumption that Ir and/or Is determinants are responsible for these associations in agreement with the fact that many of these diseases are characterized by autoimmune phenomena. However, some diseases, ankylosing spondylitis in particular, still show stronger associations with HLA-ABC than with DR antigens. Among the conditions which have been shown to be HLA-associated more recently, four deserves special mention: (i) maternal immunization against the Zwa antigen because this is a good candidate for an antigen-specific Ir gene action; (ii) IgA deficiency in blood donors because this is a non-antigen-specific immunodeficiency; (iii) idiopathic hemochromatosis and (iv) congenital adrenal hyperplasia due to 21-OH deficiency because immune mechanisms are unlikely to be involved. HLA studies and new genetic methodology have significantly advanced our knowledge about the inheritance of some diseases. Thus, HLA-B27 or a B27-associated HLA factor confers a dominant susceptibility to ankylosing spondylitis. HLA plays a definite and strong role in the susceptibility to IDDM, but simple genetic models (dominant, recessive, and intermediate) have been made unlikely on the basis of HLA results; the hypothesis that there are two different susceptibility genes within the HLA system still remains viable, but the demonstration of clinical heterogeneity and/or (better) of different pathogenetic pathways for DR3- and DR4-associated IDDM is required to substantiate it.
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PMID:HLA and disease 1982--a survey. 633 68

In most of our membranous glomerulonephritis (MGN) patients, we have studied the HLA-A, B, DR phenotype, the clearance of anti-D rhesus coated 51Cr-labelled autologous erythrocytes, and T-lymphocyte subpopulations with monoclonal antibodies (OKT3, T4, T8). The frequency of B8 antigen in 28 patients with MGN (five cases associated with lupus excluded) is 57.14 per cent versus 14.42 per cent in controls (Pc = 0.0002). In 26 patients the frequency of DR3 antigen is 65.38 per cent versus 20.27 per cent in controls (Pc = 0.00008). The half-life of sensitised erythrocytes is respectively 35.36 +/- 8.50 minutes in nine controls and 67.05 +/- 69.64 min in 18 patients with MGN. The half-life is significantly prolonged in one-third of the patients at time of exacerbation. The peripheral blood T-lymphocyte subsets study showed a significant decrease of OKT3 and OKT4 positive cell subsets. T4/T8 ratio is high during exacerbation of disease and diminishes in remission. Our data are consistent with a latent subtle genetic immunodeficiency, only expressed during acute phases of the disease.
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PMID:Immunogenetics and immunopathology of human membranous glomerulonephritis. 641 Mar 85


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