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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Infection by the human immunodeficiency virus is associated with polyclonal B cell activation and increased levels of serum IgA. In order to characterize the molecular species of serum IgA, we have measured total IgA, IgA1, and IgA2 in sera from 60 HIV-1-infected patients and 40 healthy controls. In addition, secretory IgA (S-IgA), secretory IgM (S-IgM), free immunoreactive secretory component (SC), and the distribution of monomeric and polymeric IgA were determined. The data confirm the elevation of total serum IgA levels in HIV-1-infected patients, and both IgA1 and IgA2 concentrations are elevated. Furthermore, the data show a substantial increase in serum levels of both monomeric and polymeric IgA. Serum S-IgA levels were significantly increased in CDC group II patients versus controls and more frequently elevated in CDC group IV patients. The highest S-IgA levels were found among patients with the lowest blood CD4+ cell counts. Serum S-IgA levels were not correlated with serum levels of either total IgA or polymeric IgA. Serum S-IgM levels were also increased in HIV-1-infected patients and positively correlated with serum S-IgA levels. Conversely, serum levels of free SC were not altered. An increase in serum S-IgA was not related to human hepatitis B virus infection and/or to hepatic dysfunction or to diarrhea or overt intestinal infection. The data indicate that secretory Ig (S-IgM and S-IgA), which are likely to be produced at mucosal sites, increase in the serum of HIV-1-infected patients.
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PMID:Secretory immunoglobulins in serum from human immunodeficiency virus (HIV)-infected patients. 135 13

The mechanism of the binding of IgA to the mesangium in IgA nephropathy (IgAN) is unknown. Interactions between IgA and components of the mesangial matrix may contribute. We measured by enzyme-linked immunosorbent assay the binding of serum IgA, IgG, and IgM from patients with IgAN, human immunodeficiency virus type I (HIV) infection, and healthy controls to purified native collagen types I to VI, and to an extract of normal kidney tissue. HIV infection is an appropriate disease control because of the lack of mesangial IgA deposits, despite high serum levels of IgA and IgA1-containing immune complexes. Increased levels of IgA-binding to collagen types I and V and the kidney extract were found only in IgAN. Both IgAN and HIV-infected patients had increased IgA-binding to collagen types II, III, and VI. Preabsorption of the sera with gelatin substantially reduced the IgA-binding to collagen types I to IV, but not to types V and VI. This finding suggests that the binding to collagen type V is not fibronectin-mediated, but may reflect autoantibody formation. Thus, fibronectin-mediated IgA-collagen interactions are not specific for IgAN, and their pathogenetic role is questionable. The role of IgA anti-collagen type V antibodies requires further study.
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PMID:Binding of serum immunoglobulins to collagens in IgA nephropathy and HIV infection. 140 20

Selective deficiency of serum IgA is the most common immunodeficiency in humans; when immunodeficient individuals receive blood transfusions a severe anaphylactoid reaction can develop. The present report describes such a patient. After the transfusion reaction a hemagglutination inhibition assay revealed that her blood contained less than 1.0 micrograms/ml of IgA and an anti-IgA antibody that reacted with the 2 IgA proteins, isotypes IgA1 and IgA2. Immediately after the reaction the patient's serum anti-IgA antibody titer was 1:16,384, and when reevaluated 5 weeks later it was 1:8000. All 3 of her children were shown to be IgA deficient, and 2 of them had antibodies against IgA2. This type of anaphylactoid reaction can be avoided by transfusing blood from IgA-deficient donors, frozen deglycerolized red cells, or red cells that have been washed several times to extract all IgA proteins.
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PMID:Blood transfusion reaction in a patient with immunoglobulin A deficiency. 640 58

The existence of specific probes for human genes makes it feasible to study genetic abnormalities, both inherited and acquired, at the level of the genome. In this respect, the antibody genes of man are of particular interest as they represent a multigene family expressed in many leukaemias and immunodeficiency diseases. Furthermore, selective deficiency of immunoglobulins has been described in healthy individuals. Normally, human adults express five types of immunoglobulin--IgM, IgD, IgG, IgE and IgA (defined by the class of heavy chain constant region). Subclasses are also known in IgG (IgG1, IgG2, IgG3 and IgG4) and IgA (IgA1 and IgA2) in which the immunoglobulins contain gamma 1, gamma 2, gamma 3 or gamma 4 and alpha 1 or alpha 2 CH regions, respectively. Recently, a healthy Tunisian person was described who showed abnormal patterns of immunoglobulin expression. The serum immunoglobulin of this individual, designated TAK3, was confined to IgM, IgD, IgG3, IgE and IgA2. We have now used cloned CH-gene probes to study the DNA of TAK3 as well as two brothers, also Tunisian but apparently unrelated to the individual TAK3, and who show a similar immunoglobulin abnormality. We found that in these cases there seems to have been a large chromosomal deletion which includes three gamma genes, an alpha gene and a pseudo-epsilon gene. This deletion accounts for the simultaneous absence of certain H-chain subclasses. These results illustrate that the human immunoglobulin gene locus is capable of undergoing rapid change, which is particularly apparent within small populations in which consanguinity is common.
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PMID:Inherited deletion of immunoglobulin heavy chain constant region genes in normal human individuals. 681 43

A flow cytometry-based assay for detection of immunoglobulin (Ig) class and subclass antibodies in human serum or plasma was developed. With use of this procedure, the presence and relative frequency of antibody activity in the Ig classes and subclasses (IgA1, IgA2, IgD, IgE, IgG1, IgG2, IgG3, IgG4, and IgM) to human immunodeficiency virus type 1 (HIV-1) proteins (gp160, gp120, p66, and p24) was determined in serum or plasma from a cohort of 47 HIV-1-infected, pregnant women. Antibody activity in each of the classes and subclasses was found with differences in frequency depending on the Ig class/subclass and the HIV-1 protein. IgG1 antibodies were the most frequently reactive Ig class/subclass to each protein. Intermediate frequencies of reactivity were found in IgA1, IgG2, IgG3, and IgM class and subclasses and antibodies of the IgA2, IgE, and IgG4 class/subclass the least frequently detected. An unexpected finding was the presence of IgD antibodies to HIV-1 proteins in approximately 50% of the individuals. The distributions of Ig class/subclass antibodies to the different HIV-1 proteins were compared in sera from 14 mothers giving birth to infants who were determined to be HIV-1 infected with sera from 25 individuals whose infants were not infected. Sera from transmitting mothers contained a broader distribution of class and subclass antibodies compared to sera from nontransmitting women. The single most frequent antibody-antigen combination that was found in the transmitting mother was IgG2-gp160.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Immunoglobulin class and subclass antibodies to HIV proteins in maternal serum: association with perinatal transmission. 751 62

To determine whether defects in mucosal immunity were associated with invasive disease caused by a mucosal pathogen, Streptococcus pneumoniae, levels of salivary immunoglobulins and nonspecific immune factors were compared in subjects with human immunodeficiency virus type 1 (HIV-1) infection and in HIV-1-seronegative subjects with and without pneumococcal bacteremia. The IgA2 subclass may be of particular importance because S. pneumoniae produces IgA1 protease, which cleaves IgA1 but not IgA2. Levels (37-56 micrograms/mL) and proportions (11%-17%) of IgA2 were similar among groups. Serotype-specific capsular salivary IgA was present in a minority of patients with acute bacteremia. Levels of lactoferrin were increased with bacteremia. Neither selective mucosal IgA2 deficiency nor impaired nonspecific upper respiratory mucosal responses were associated with invasive pneumococcal disease during HIV-1 infection; thus, other defects in mucosal cellular responses and systemic immunity may predispose HIV-1-infected patients to invasive pneumococcal disease.
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PMID:Impact of Streptococcus pneumoniae bacteremia and human immunodeficiency virus type 1 on oral mucosal immunity. 762 7

Most patients with common variable immunodeficiency (CVI) have normal numbers of circulating B cells but low concentrations of serum Ig. To determine if the hypogammaglobulinemia is caused by an intrinsic B cell defect, we studied B cell function of 22 CVI patients. Cultured B cells from all CVI patients underwent normal proliferation and synthesized normal quantities of IgE in the presence of anti-CD40 and IL-4. If cultured with anti-CD40 and IL-10, four patterns of Ig isotype synthesis were observed. Six CVI patients produced normal amounts of IgM, IgG, and IgA. Four patients produced normal quantities of IgM and IgG. Of the remaining 12 patients who failed to synthesize IgG and IgA, 8 produced normal and 4 synthesized decreased amounts of IgM. Analysis of the IgG subclasses produced by 10 patients with IgG-secreting B cells revealed that IgG4 was the most affected subclass, followed by IgG2; synthesis of IgG3 and IgG1 remained normal. Similarly, in the six IgA producing patients, IgA2 was more often affected than IgA1. The hierarchy of Ig isotype and subclass synthesis corresponds to Ig heavy chain constant region gene location on chromosome 14. Thus, circulating B cells of CVI patients are committed to synthesize one or more Ig isotypes or subclasses, and under proper conditions can proliferate, mature into Ig-secreting cells, and undergo class switch to IgE.
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PMID:Activated B cells from patients with common variable immunodeficiency proliferate and synthesize immunoglobulin. 769 Jul 75

This study was performed in 27 HIV-1+ children to characterize the IgA hyperglobulinaemia observed in the serum during the course of HIV-1 infection. By contrast with serum IgG, which increased very early, IgA elevation was related to the decrease of CD4+ cell percentage. It was demonstrated that IgA1 subclass increased selectively. Secretory IgA (SIgA) and IgA and IgG activity to gliadin, bovine serum albumin (BSA) and at a lower level to casein could be detected in the serum at the early stages of HIV infection, but SIgA levels and IgA activity to gliadin further increased during the course of immunodeficiency. By contrast, IgA and IgG activity to tetanus toxoid did not change. These data demonstrate that the hyper IgA, closely related to the degree of immunodeficiency, could be due in part to a disturbance of the gut mucosal immune system. Moreover, impaired intestinal immunity seems to appear very early, and to progress during the course of paediatric HIV-1 infection.
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PMID:Early impairment of gut mucosal immunity in HIV-1-infected children. 791 75

In intestinal fluid samples from 39 human immunodeficiency virus type 1 (HIV-1)-infected patients, IgA and IgG levels were equivalent, whereas in 10 controls, IgA levels were significantly higher than those of IgG (P < .05). Intestinal IgA in patients contained predominantly monomeric IgA1, whereas IgA1 and IgA2 subclass levels in controls were nearly equivalent and primarily polymeric. The predominance of IgG and monomeric IgA1 in mucosal fluid samples from HIV-1-infected patients suggests exudation of serum immunoglobulins into the intestine. The decreased proportion of mucosal plasma cells producing IgA and IgA2 in the HIV-1-infected patients (P < .01) may also contribute to the abnormal intestinal immunoglobulin levels. Intestinal IgG reacted with most HIV-1 antigens, whereas specific IgA was present in only 10 of 17 patients and reacted with only envelope (gp120 and gp160) and, less often, core (p17 and p24) antigens. Aberrant mucosal antibody responses and decreased integrity of the mucosal barrier may contribute to the intestinal dysfunction and infections that characterize HIV-1 infection.
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PMID:Intestinal mucosal immunoglobulins during human immunodeficiency virus type 1 infection. 803 14

The humoral immune system of the small intestine of 17 patients with common variable immunodeficiency (CVID) was studied by immunohistology using antibodies specific for IgA1,2, IgM, IgG1-4, the J chain and the secretory component (SC). IgA1,2+, IgG2+ and IgM+ lamina propria B cells were totally lacking in 65% (11/17), 41% (7/17) and 18% (3/17) of CVID patients, respectively. One patient exhibited an isolated IgA1 subclass deficiency. The proportion of plasma cells in conventionally stained histological sections of the same intestinal biopsies showed a close correlation with the numbers of IgA+ and IgM+ cells. Considerable numbers of J chain-synthesizing cells were present in all patients with CVID, indicating the presence of early B cells unable to differentiate into immunoglobulin-producing plasma cells. Most of the patients with intestinal IgA and/or IgM defects strongly expressed the SC in their enterocytes, suggesting an immunoglobulin-independent regulation of the SC. Clinically, only CVID patients with intestinal IgA defects developed intestinal infections with Giardia lamblia, Campylobacter jejuni or Candida albicans. The outcome of in vitro immunoglobulin synthesis assays with peripheral blood lymphocytes did not predict the presence or absence of the respective isotype-producing B cells in the intestinal lamina propria. Thus, immunohistological examinations of intestinal biopsies are required to determine the extent of mucosal immunodeficiency in CVID patients.
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PMID:Intestinal B cell defects in common variable immunodeficiency. 830 94


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