Activation of IgA-Specific Switch T Cells in Patients with IgA Nephropathy1

Sakai, Hideto; Endoh, Masayuki; Yano, Naohiro; Kashem, Abul; Nomoto, Yasuo

doi:10.1159/000422401

Cited by 34 publications

(45 citation statements)

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“…Thus, the high serum levels of polymeric IgA. frequently observed in patients [5], but not in the family members (probably due to a good clear ance of IgA by the liver [24, 25]), might induce an increased number of T cells with surface membrane receptors for IgA (Ta cells), such as described in mice with IgA-secreting myelomas [26], These Ta cells seem to have an IgA-specific helper T activity [27], Preliminary experiments in our laboratory further favor the idea that the T cell abnormalities could be a secondary event, since serum from patients with IgA nephropathy induces an increased production of IgA synthesis by normal control lymphocytes, after in vitro polyclonal stimulation, and T cell derangements similar to those described in patients with this nephropathy [8][9][10], Since no family member studied throughout I year presented microhematuria, the relation between the cel lular abnormalities found in the patients' relatives and the appearance of IgA nephropathy is uncertain, and it does not seem that they can by themselves explain the pathogenesis of this disease. It is possible that the persis tence of high serum levels of polymeric IgA could be an important factor.…”

Section: Discussionsupporting

confidence: 54%

“…Al though the role of immune cells has received little atten tion in this entity, the existence of an increase in the synthesis of IgA by circulating mononuclear cells and abnormalities in the ConA-generated IgA suppressor cell function [8,9], as well as the prevalence of T helper sub set, has recently been described [10]. We have thus cho sen these assays to evaluate the immunoregulatory func tion in healthy relatives.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Immunological Abnormalities in Healthy Relatives of Patients with IgA Nephropathy

Egido¹,

Blasco²,

Sancho³

et al. 1985

Am J Nephrol

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Patients with IgA nephropathy have elevated serum levels of polymeric IgA, probably due to an increase in their synthesis by peripheral blood mononuclear cells, and specific abnormalities in the immunoregulation of IgA. The existence of familial cases of IgA nephropathy, as well as the published association of this nephropathy with some antigens of the HLA system, decided us to test the hypothesis that some of these alterations might be genetically controlled. For this reason we studied some of these immunological assays in 25 first-degree relatives of 7 patients with IgA nephropathy and 22 control subjects matched for age and sex. An abnormal immunological assay was found in at least 1 relative of all families examined. Thus, 16 of 25 relatives had a significant increase in the percentage of polymeric IgA-producing cells after 7 days of culture in the presence of pokeweed mitogen. Some derangement in the concanavalin A generation of specific IgA suppressor cells was found in 11 out of 25 relatives. These results are, though in lower frequency, similar to those seen in patients and suggest that the IgA-immunological abnormalities observed are genetic markers, even if they cannot by themselves explain the pathogenesis of the IgA nephropathy. The absence of IgA immune complexes seen in relatives as well as their high prevalence in patients suggest that in predisposed subjects other factors (genetic or not) are required for the development of IgA nephropathy.

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Section: Discussionsupporting

confidence: 54%

Section: Discussionmentioning

confidence: 99%

Immunological Abnormalities in Healthy Relatives of Patients with IgA Nephropathy

Egido¹,

Blasco²,

Sancho³

et al. 1985

Am J Nephrol

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“…In the human syndrome, immune complexes containing polymeric IgA are deposited in the glomerular mesangium, and there is evidence of a reduction in IgAspecific T suppressor cells and an increase in IgAspecific T helper cells. 43 - 45 Neither of these last findings has been documented to date in SHR.…”

Section: Discussionmentioning

confidence: 89%

Elevation of plasma immunoglobulin A in the spontaneously hypertensive rat.

Chen

Schachter

1993

Hypertension

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Prior studies describe deficiencies of T-cell-mediated immunity in the spontaneously hypertensive rat (SHR) strain of Okamoto and Aoki. This report describes an alteration of humoral immunity: elevation of the plasma concentration of immunoglobulin (Ig) A and of circulating IgA autoantibodies to single-stranded DNA, double-stranded DNA, and thyroglobulin. The increased plasma IgA levels are evident in prehypertensive SHR, hence not secondary to the hypertension, and they result mainly from increments in polymeric IgA. Plasma IgA content also varied concordantly with the level of systolic blood pressure as influenced by age (older>younger) and gender (male>female) in both the SHR and control Wistar-Kyoto rat strains. Strain differences in plasma IgG or IgM were not observed. Studies of peripheral blood lymphocytes indicate that increased production of IgA is one mechanism for the increment in plasma content. The number of blood lymphocytes capable of producing IgA in vitro in response to the mitogen lipopolysaccharide is increased in SHR. When cultured in the absence or presence of lipopolysaccharide, peripheral blood lymphocytes of SHR secrete more IgA in vitro than do cells of the control strain. No significant strain differences in biliary or renal excretion of IgA were observed. The observed alterations of IgA in the SHR either are causative factors in the development of the hypertension or are the products of an epiphenomenon in which IgA and blood pressure are affected separately, but in parallel, by causative factors related to rat strain, age, and gender.

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“…Their results, however, were inconclusive. They reported a decreased suppressor T cell activity specific for IgA in this entity (27), although such a defect could be secondary to increased levels of serum IgA and/or an increased proportion of IgA-bearing lymphocytes. More recently (28) they found an increased number of IgA-specific helper T cells.…”

Section: Discussionmentioning

confidence: 93%

“…Sakai et a1 (27,28) activity of suppressor and helper T lymphocytes specific for IgA production in patients with IgA nephropathy, considered by several authors to be a disease with a pathogenic mechanism similar to that of HSP (6,ll). Their results, however, were inconclusive.…”

Section: Discussionmentioning

confidence: 99%

Increased IgA‐producing cells in the blood of patients with active henoch‐schönlein purpura

Casanueva

Rodríguez‐Valverde

Merino

et al. 1983

Arthritis & Rheumatism

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Peripheral blood lymphocytes (PBL) producing IgA, IgM, and IgG, both spontaneously and after pokeweed mitogen stimulation in cell culture, were determined by a protein A hemolytic plaque assay in 20 children with active Henoch‐Schönlein purpura (HSP), 42 with inactive disease, 22 normal controls of the same ages, and 18 children with upper respiratory tract infections (URTI). The geometric mean of circulating IgA‐producing cells in active HSP (1,016 \documentclass{article}\pagestyle{empty}\begin{document}$\[\begin{array}{l} \times \\ \div \\ \end{array}\] $\end{document} 1.55 cells/106 PBL) was increased when compared with the group with inactive disease (P < 0.001), normal controls (P < 0.001), and children with URTI (542 \documentclass{article}\pagestyle{empty}\begin{document}$ \[\begin{array}{l} \times \\ \div \\ \end{array}\] $\end{document} 2.03 cells/106 PBL, P < 0.05). The number of circulating IgM‐producing cells was slightly increased in active HSP (260 \documentclass{article}\pagestyle{empty}\begin{document}$ \[ \begin{array}{l} \times \\ \div \\ \end{array}\] $\end{document} 2.65 cells/106 PBL) and URTI (256 \documentclass{article}\pagestyle{empty}\begin{document}$ \[\begin{array}{l} \times \\ \div \\ \end{array}\] $\end{document} 3.16 cells/106 PBL). Both values were higher than those found in the group with inactive disease (113 \documentclass{article}\pagestyle{empty}\begin{document}$ \[\begin{array}{l} \times \\ \div \\ \end{array}\] $\end{document} 2.26 cells/106 PBL, P < 0.01). There were no significant differences among the 4 groups in the number of circulating IgG‐producing cells. The number of cells producing each type of immunoglobulin after in vitro stimulation with pokeweed mitogen was similar in patients with active HSP, normal controls, and the group with inactive disease. These data demonstrate a selective increase in the number of circulating IgA‐producing cells only during disease activity, and add further support to a possible pathogenic role of this immunoglobulin in HSP.

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Activation of IgA-Specific Switch T Cells in Patients with IgA Nephropathy1

Cited by 34 publications

References 0 publications

Immunological Abnormalities in Healthy Relatives of Patients with IgA Nephropathy

Immunological Abnormalities in Healthy Relatives of Patients with IgA Nephropathy

Elevation of plasma immunoglobulin A in the spontaneously hypertensive rat.

Increased IgA‐producing cells in the blood of patients with active henoch‐schönlein purpura

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