Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q00604 (X-linked)
 16,883 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

(CBA/N female x BALB/c male)F1 male mice carry an X-linked defect, originating from CBA/N mice, which renders them unable to generate an antibody response to SSS-III. Histocompatible (BALB/c female x CBA/N male) reciprocal F1 male hybrids do not carry the X-linked defect and therefore generate a readily detectable PFC response to SSS-III, which can be adoptively transferred into nonresponding reciprocal F1 male mice. In the present work, we show that this adoptive response could be inhibited in recipient (CBA/N female x BALB/c male)F1 male nonresponding mice in which low dose paralysis had been induced. Evidence is presented which indicates that such suppression is of host rather than donor cell origin. The capacity to develop low-dose paralysis, a phenomenon that is antigen specific and has been attributed to the action of suppressor T cells, indicates that nonresponding (CBA/N female x BALB/c male) F1 males (and presumably the CBA/N progenitor strain) have the ability to recognize this antigen. Furthermore, since these animals fail to make a serum antibody response to SSS-III, the signal that activates suppressor T cells cannot be circulating antibody or antigen-antibody complexes. These findings are most consistent with the view that low-dose paralysis of the response to SSS-III is not dependent on antibody-mediated feedback inhibition; rather, it is an active process mediated by suppressor T cells.
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PMID:Generation of low-dose paralysis in the absence of the ability to secrete antibody. 2 65

Spleen cells from CBA/N mice with an X-linked B cell defect were examined for their ability to form antibody in vitro after stimulation with the T-independent antigen TNP-LPS. In contradistinction to their failure to respond to some conventional T-independent antigens such as type III pneumococcal polysaccharide or DNP-AECM-Ficoll, spleen cells from (CBA/N X DBA/2)F1 male mice were able to make a specific anti-TNP PFC response after culture with TNP-LPS. Their response differed from that of phenotypically normal (CBA/N X DBA/2)F1 female littermate spleen cells in that more TNP-LPS was required to elicit the peak anti-TNP response and the anti-TNP antibody secreted by F1 male cells was of lower avidity than that of F1 female cells. The polyclonal antibody response to unsubstituted LPS did not differ substantially between normal and defective B cells. Tnymus-derived cells were not required for the TNP-LPS response by either F1 male or female cells. We conclude that CBA/NB cells can respond to certain T-independent antigens that are able either to induce a very strong activating signal upon ligand-surface receptor interaction and/or to stimulate immature B cells (with a characteristic high surfact immunoglobulin profile) which fail to respond to antigens like DNP-AECM-Ficoll.
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PMID:In vitro responses of CBA/N mice: spleen cells of mice with an X-linked defect that precludes immune responses to several thymus-independent antigens can respond to TNP-lipopolysaccharide. 78 72

The molecular bases of the X-linked immunodeficiency diseases remain largely undetermined. Two of the genes involved in these diseases have been isolated, namely the genes for X-linked chronic granulomatous disease and properdin deficiency, and substantial progress has now been made in identifying the genes which are defective in the other five diseases, Wiskott-Aldrich syndrome, X-linked severe combined immunodeficiency, X-linked agammaglobulinaemia, X-linked hyper-IgM and X-linked lymphoproliferative syndrome. We review here the nature of the diseases, progress made in identifying and isolating the genes involved and the prospects for improved prenatal detection, carrier status determination and treatment of these life-threatening conditions.
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PMID:The molecular basis of X-linked immunodeficiency disease. 152 25

Properdin is a serum protein belonging to the alternative pathway of complement activation whose absence is often associated with fatal bacterial infections. Properdin deficiency segregates with an X-linked recessive pattern and its position has been recently refined by genetic linkage analysis to the proximal part of the X-chromosome short arm near the OTC and DXS7 loci. We have hybridized an 0.8-kb genomic clone encoding part of the human properdin gene to a panel of somatic cell hybrids retaining different portions of the human X chromosome and thereby localized the probe to Xcen-Xp21.1. Furthermore, in situ hybridization of the same probe to replication banded metaphase chromosomes refined this localization to the region Xp11.23-Xp21.1 (with a peak grain distribution in the region equivalent to Xp11.4). As OTC and DXS7 map to Xp21.1 and Xp11.3, respectively, the data presented here strongly suggest that the X-linked deficiency syndrome is due to a defect in the locus encoding the structural properdin gene or in a physically close regulatory locus.
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PMID:Localization of the properdin structural locus to Xp11.23-Xp21.1. 257 30

A selective deficiency of properdin (P) was identified in a 58-year-old male and in his 29-year-old nephew, both of whom were clinically healthy. As determined by different immunochemical methods P at low concentrations (about 2 mg/l) was detectable in serum and plasma. Three female relatives, including the mother and daughter of one of the P-deficient males showed moderately low P concentrations. The findings clearly suggested that the deficiency was inherited as an X-linked trait. Three males belonging to another family with P deficiency also showed detectable P concentrations. By contrast, no P (less than 0.1 mg/l) was found in 8 males belonging to three other families. We suggest that there are two variants of X-linked P deficiency: P deficiency type 1, characterized by extremely low P concentrations (less than 0.1 mg/l); and P deficiency type 2 recognizable by P concentrations of about 2 mg/l. The P detected in P deficiency type 2 had subunits of normal molecular weight (52 kilodaltons), but eluted in a lower molecular weight range than did the P of normal serum, either on gel filtration (Ultrogel AcA 22) or on size exclusion chromatography (TSK-4000). The evidence suggested that the P concentration may be one determinant of P oligomer formation. P-deficient serum type 2 did not support fluid phase C3 cleavage in the presence of such alternative pathway activators as inulin and zymosan, nor did it support efficient lysis of guinea pig erythrocytes in agarose gel. By contrast, rabbit erythrocytes were efficiently lyzed, but at a slow rate. P-deficient serum type 1 did not support lysis of rabbit erythrocytes in the assay system used. The reaction was clearly promoted by very low concentrations of purified P. Partially purified P from a male with P deficiency type 2 was shown to be hemolytically active. Further evidence of P function in P deficiency type 2 was obtained by using IgG-presensitized serogroup W-135 meningococci in an alternative pathway-mediated serum bactericidal assay.
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PMID:A second variant of properdin deficiency: the detection of properdin at low concentrations in affected males. 314 Nov 11

The ability of B cells to respond to TNP-Ficoll has been shown to correlate with their ability to respond to T cell-replacing factor (TRF). The present study analyzed the relationship of TNP-Ficoll-responsive B cells to a TRF-responsive B cell subpopulation. The B cells from normal, unprimed mice responded to TNP-Ficoll in the presence of accessory cells. Such responses were notably augmented by the addition of TRF derived from a monoclonal T cell hybridoma, B151K12(B151-TRF). Interestingly, B cells of mutant X-linked immunodeficient DBA/2Ha which failed to respond to B151-TRF gave anti-TNP PFC responses to TNP-Ficoll comparable to those of normal mice, depending on the presence of accessory cells. However, under this condition, the addition of B151-TRF did not augment the TNP-Ficoll responses. One explanation of the augmentation of TNP-Ficoll response by TRF for the B cells from nondefective mice was that two distinct B cell subpopulations exist which differ in their respective activation requirement for TRF and accessory cells. To examine this possibility, syngeneic accessory cells were pulsed with TNP-Ficoll and were assayed for their ability to activate normal B cells in the presence or absence of B151-TRF. The results revealed that TNP-Ficoll-pulsed accessory cells were able to induce primary anti-TNP PFC responses in normal B cells to the same magnitude as soluble TNP-Ficoll. However, these B cell responses induced by the TNP-Ficoll-pulsed accessory cells were not augmented by the addition of B151-TRF to the culture. These results support the notion that two distinct TNP-Ficoll-responsive B cell subpopulations exist; one requires accessory cell-B cell interaction to be activated by TNP-Ficoll but fails to respond to TRF, and the other can be activated by TRF in a totally accessory cell-independent manner.
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PMID:Evidence for existence of two distinct TNP-Ficoll-responsive B cell subpopulations preferentially reactive either to a T cell-replacing factor (B151-TRF) or to a signal from accessory cells. 348 39

Antigens of Streptococcus mutans 6715 (alternatively designated serotype g Streptococcus sobrinus), including whole cells (WC g), cell walls (CW g), peptidoglycan (PG g) and serotype carbohydrate (Ml g) were coupled with trinitrophenyl (TNP), and the nature of the immune response to each immunogen was determined in normal and X-linked immunodeficient (xid) murine spleen cell cultures. Responses to TNP-WC g, -CW g and -PG g and to the classical type 1 antigen TNP-Brucella abortus occurred in both xid and normal splenic cultures, while TNP-Ml g only triggered immune responses in normal spleen cell cultures, suggesting that the former three antigens are type 1 and the latter type 2. Further support for the type 2 nature of TNP-Ml g was the finding that Peyer's patch cell cultures from both xid (which contain mature B cells) and normal mice supported responses to TNP-Ml g and TNP-Ficoll, while xid splenic cultures failed to support responses to either type 2 antigen. The three type 1 TNP-S. mutans antigens induced responses in nude spleen cell and in purified splenic B cell cultures, but required T cells for in vitro responses to lower doses of immunogen. On the other hand, TNP-Ml g induced anti-TNP PFC responses at several antigen concentrations in purified B cell cultures, without requirement for added T cells. These studies show that the intact S. mutans cell, as well as CW g and PG g, acts as a T cell-dependent (TD) type 1 antigen, while the serotype carbohydrate (Ml g) induces a T cell-independent (TI) type 2 response. Thus, the intact bacterium is a TD type 1 antigen, whereas its purified components are either type 1 or type 2 antigens and differ significantly in terms of their T cell dependence.
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PMID:Haptenated streptococcal antigens elicit either T cell-dependent type 1 or T cell-independent type 2 immune responses. 349 65

We report a family in which three males in two generations had meningococcal infections; one of them died. Hemolytic activity of the alternative complement pathway in the two survivors and in one healthy boy belonging to the family was reduced, as measured in a kinetic system. These three individuals had 10-11% of normal properdin concentration in plasma, as measured by a catching ELISA method, while the other complement components were normal. Hemolytic complement activity was normalized when purified properdin was added. The data are compatible with an X-linked mode of inheritance of properdin deficiency.
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PMID:Congenital properdin deficiency and meningococcal infection. 360 46

A nine-year-old white boy with recurrent pneumococcal bacteremia is described. His serum had no hemolytic activity in either the classic or alternative complement pathways. Absence of classic pathway activity was secondary to a homozygous deficiency of C2. The parents had half-normal levels of C2, compatible with an autosomal recessive mode of inheritance. Measurement of serum properdin levels by radial immunodiffusion and enzyme-linked immunoabsorbent assay revealed a profound deficiency in the patient, normal levels in the father, and half-normal levels in the mother, suggesting X-linked inheritance of the deficiency. Addition of purified properdin to the patient's serum fully reconstituted the alternative pathway function. This patient's unique combination of inherited deficiencies of properdin and C2 is a likely explanation for his susceptibility to bacterial infection.
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PMID:Inherited deficiency of properdin and C2 in a patient with recurrent bacteremia. 382 29

Three males in a large family showed a selective deficiency of properdin (P). One of the P deficient individuals died from a fulminant infection with Neisseria meningitidis group C. The family history revealed three previous cases of similar infections with a fatal outcome. The deficiency did not appear to be associated with repeated bacterial infections. The pattern of inheritance suggested an X-linked mode of transmittance. However, heterozygous carriers were not clearly distinguished in the family. P deficient serum supported immune haemolysis in a normal fashion. Alternative pathway functions, such as the activation of C3 by inulin or zymosan, lysis of guinea-pig erythrocytes in agarose gel and opsonization of endotoxin coated oil particles, were grossly impaired in P deficient serum while efficient C3 activation was produced by addition of cobra venom factor.
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PMID:Properdin deficiency in a family with fulminant meningococcal infections. 715 27


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