scholarly journals Alternative Complement Pathway Is Activated and Associated with Galactose-Deficient IgA1 Antibody in IgA Nephropathy Patients

2021 ◽  
Vol 12 ◽  
Author(s):  
Yen-Ling Chiu ◽  
Wei-Chou Lin ◽  
Kai-Hsiang Shu ◽  
Yi-Wen Fang ◽  
Fan-Chi Chang ◽  
...  
Keyword(s):  
Renal Function ◽  
Disease Activity ◽  
Iga Nephropathy ◽  
Plasma Levels ◽  
Clinical Severity ◽  
Alternative Complement Pathway ◽  
Complement Factor ◽  
Complement Pathway ◽  
Pathway Activation ◽  
Alternative Complement

BackgroundGalactose-deficient IgA1 (Gd-IgA1) and alternative complement pathway activation are considered to be involved in the pathogenesis of IgA nephropathy (IgAN). Nevertheless, the relationships between alternative pathway activation and disease activity or Gd-IgA1 level remains unclear.MethodsNinety-eight biopsy-diagnosed IgAN, twenty-five primary focal segmental sclerosis (FSGS) patients and forty-two healthy individuals were recruited in this study. Among them, fifty IgAN patients received immunosuppression. Follow-up blood samples at 1 and 3~6 months after immunosuppression were collected. Plasma levels of complement C5a, factor Ba and Gd-IgA1 were measured and analyzed. Immunostaining for complement was performed in twenty-five IgAN and FSGS patients.ResultsAt baseline, IgAN patients had higher levels of plasma C5a, factor Ba and Gd-IgA1 than control subjects. Gd-IgA1 levels positively correlated with plasma C5a and factor Ba. In addition, levels of factor Ba and Gd-IgA1 were positively associated with proteinuria and negatively associated with renal function. Immunostaining revealed positive staining for factor Bb and C3c in glomeruli in IgAN patients, but not in FSGS patients. At baseline, patients receiving immunosuppression had more severe proteinuria and higher factor Ba. After 6 months, eGFR declined and proteinuria persisted in patients without immunosuppression. In contrast, patients who received immunosuppression exhibited decreased plasma levels of C5a, factor Ba, and Gd-IgA1 as early as 1 month after treatment. Proteinuria decreased and renal function also remained stable 6 months after immunosuppression.ConclusionsOur results indicate a close relationship between alternative complement pathway activation, Gd-IgA1 concentration and clinical severity of IgAN. Level of complement factor B may be a potential marker for disease activity and therapeutic target in IgAN patients.

scholarly journals Identification of human complement factor H as a chemotactic protein for monocytes

1997 ◽  
Vol 326 (2) ◽  
pp. 377-383 ◽  
Author(s):  
Karim NABIL ◽  
Bertrand RIHN ◽  
Marie-Claude JAURAND ◽  
Jean-Michel VIGNAUD ◽  
Jean RIPOCHE ◽  
...  
Keyword(s):  
Malignant Cell ◽  
Factor H ◽  
Alternative Complement Pathway ◽  
Complement Factor H ◽  
Complement Factor ◽  
Complement Pathway ◽  
Pathway Activation ◽  
Chemotactic Protein ◽  
Alternative Complement ◽  
Cellular Immune

We used chromatographic separation to purify to homogeneity a monomeric monocyte chemotactic protein of 150 kDa contained in mesothelioma pleural effusions. It was identified by N-terminal amino acid sequencing and immunoblotting as complement factor H, an inhibitor of the alternative complement pathway. Specific antibodies against factor H inhibited the monocyte chemotactic activity of the purified protein, which was most active at 10 nM. Factor H is a restrictive factor of alternative complement pathway activation. The new chemotactic function assigned to factor H in recruiting monocytes to the mesothelioma site might contribute to malignant cell phagocytosis via the iC3b/complement receptor type 3 pathway. These functions link the humoral and cellular immune systems.

scholarly journals Activation of the guinea pig alternative complement pathway by mouse IgA immune complexes.

1982 ◽  
Vol 155 (1) ◽  
pp. 231-247 ◽  
Author(s):  
G Pfaffenbach ◽  
M E Lamm ◽  
I Gigli
Keyword(s):  
Guinea Pig ◽  
Immune Complexes ◽  
Alternative Pathway ◽  
Fluid Phase ◽  
Alternative Complement Pathway ◽  
Complement Pathway ◽  
Myeloma Protein ◽  
Pathway Activation ◽  
Alternative Complement ◽  
Iga Immune Complexes

Activation of the complement system by IgA was investigated with immune complexes containing a mouse IgA myeloma protein with specificity for phosphorylcholine linked to bovine serum albumin (PC-BSA). These IgA anti-PC-BSA immune complexes activated the alternative complement pathway in mouse and guinea pig serum, while human complement was not affected. The activation proceeded with consumption of C3 but little or no consumption of C5. C3 did not bind to the IgA immune complexes during complement activation although it did bind covalently to IgG immune complexes. It is suggested that IgA immune complexes do not supply a suitable surface for C3 binding and effective alternative pathway convertase assembly; therefore, cleavage is limited and occurs primarily in the fluid phase. Without C3 binding, C5 cleavage does not occur nor can the alternative pathway activation proceed to the amplification step.

Sign in / Sign up

Export Citation Format

Share Document