Dataset Information

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

ABSTRACT:

Background

Galactose-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.

Methods

Ninety-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.

Results

At 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.

Conclusions

Our 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.

SUBMITTER: Chiu YL

PROVIDER: S-EPMC8223746 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Background and objectivesIncreased circulating galactose-deficient IgA1 and subsequently complement activation both play important roles in the pathophysiology of IgA nephropathy. However, their relationship to disease severity and progression remains unclear.Design, setting, participants, & measurementsWe assessed 1210 participants in a cohort study of biopsy-proven IgA nephropathy at Peking University First Hospital. Plasma concentrations of galactose-deficient IgA1 and complement component C3 were measured at the time of biopsy. We tested associations of galactose-deficient IgA1 and galactose-deficient IgA1/C3 ratio with CKD progression event, defined as ESKD or 50% decline in eGFR, using Cox proportional hazards models and restricted cubic splines.ResultsAfter a median follow-up of 43 months (interquartile range, 24-76 months), 172 (14%) participants reached the CKD progression event. The association of galactose-deficient IgA1 levels and CKD progression event showed a nonlinear relationship. The risk of CKD progression events was greater with higher plasma galactose-deficient IgA1 levels but reached a plateau when galactose-deficient IgA1>325 U/ml, whereas the risk of CKD progression events monotonically increased with higher galactose-deficient IgA1/C3 ratio. After adjustment for traditional risk factors (demographics, eGFR, proteinuria, hypertension, Oxford pathologic score, and corticosteroids/immunosuppressive therapy), higher levels of galactose-deficient IgA1/C3 ratio were independently associated with CKD progression event (per natural log-transformed [galactose-deficient IgA1/C3], hazard ratio, 2.03; 95% confidence interval [95% CI], 1.25 to 3.29; P=0.004). In reference to the first quartile of the galactose-deficient IgA1/C3 ratio, hazard ratios were 1.71 (95% CI, 1.01 to 2.89) for the second quartile, 1.55 (95% CI, 0.91 to 2.63) for the third quartile, and 2.17 (95% CI, 1.33 to 3.56) for the fourth quartile.ConclusionsIn IgA nephropathy, plasma galactose-deficient IgA1/C3 ratio was associated with CKD progression event independent of clinical and biopsy characteristics.

Dataset Information

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

Background

Methods

Results

Conclusions

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Dataset Information

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

Background

Methods

Results

Conclusions

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

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