Complement activation and regulation in human glomerulonephritis

Moseley, Hannah L. (1981) Complement activation and regulation in human glomerulonephritis. PhD thesis, University of Glasgow.

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This study was designed to examine closely the extent and means of activation of the complement system in human GN. In order to do this, renal biopsy material was obtained from 104 patients. Each of these biopsies fell into one of the following distinct pathological categories of glomerulo-nephritis (GN); membranous GN (MGN), membranoproliferative GN (MOGN), focal GN (GN), Henoch-Schonlein nephritis (HSN), systemic lupus erythematosus (SLE) and minimal change nephrotic syndrome (MCNS). The biopsies were examined for the presence of immunoglobulins, classical and alternative pathway components, C3 and C5 and the serum concentrations of the complement proteins, at the time of the biopsy, were also measured. There was evidence of extensive complement activation in all disease groups with the exception of MCNS and deposition of C3 was apparent in all MPGN and SLE biopsies and at least 89% of MGN, FGN and HSN biopsies. The evidence presented in this study suggests that, in MGN and SLE, the complement system was activated primarily by immune complexes involving IgG antibodies via the classical pathway since more biopsies were positive for classical than alternative pathway components and there were significant correlations between the intensities of depositions of C3 and IgG. Properdin deposition was frequently present in SLE and was also found in a small number of MGN biopsies suggesting that activation of the alternative pathway may also be involved in these two diseases. The intensity of activation was greater in SLE than in MGN with high intensities of deposition and reduced serum concentrations of complement proteins. In MPGN, FGN and HSN both pathways of activation were involved and although in MPGN and HSN more biopsies were positive for alternative rather than classical pathway components and in FGN the converse was true, correlation studies, comparing the intensities of deposition of classical and alternative pathway components with those of C3, were unable to distinguish which pathway was primarily responsible for C3 catabolism. MCNS was included in this study of represent a control group and evidence of activation of complement was found, only weekly, in two biopsies. Activation of the complement system is known to be under the control of several plasma proteins and the role of these proteins had not been previously assessed in GN. It was considered possible that the complement activation apparent in almost all types of GN and intense in some may have been the result of a breakdown in the mechanism for controlling complement activation. In order to examine this possibility, the deposition of three control proteins of complement activation, CI-inhibitor (CI-INH), C3b inactivator (C3bINA) and B1H globulin was studied and the serum concentrations of these proteins measured. The serum concentrations of control proteins were seldom reduced with low serum levels of C3bINA in the serum from four patients and low B1H levels in the serum from only one patient and although the functional activity of the proteins was not measured there is no evidence to suggest that complement activation was in general due to acquired or a genetic deficiency of control proteins. From the results presented in this study there is therefore little evidence to suggest that activation of the complement system in human GN is the result of a deficiency in regulation of complement. (Abstract shortened by ProQuest.).

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Keywords: Physiology.
Subjects: Q Science > QP Physiology
Colleges/Schools: College of Medical Veterinary and Life Sciences
Supervisor's Name: Whaley, Dr. Keith
Date of Award: 1981
Depositing User: Enlighten Team
Unique ID: glathesis:1981-72150
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 17 May 2019 12:46
Last Modified: 13 Oct 2022 14:38
Thesis DOI: 10.5525/gla.thesis.72150

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