Anti-ETAR, Anti-CXCR3 Antibodies Linked to IgA Nephropathy, Lupus Nephritis Prognosis

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Anti-endothelin A receptor (ETAR) and anti-C-X-C motif chemokine receptor 3 (CXCR3) antibodies may play an important role in predicting the disease course of IgA nephropathy (IgAN) and lupus nephritis, according to findings from a recent study.¹

Results suggest the potential prognostic value of the non-human leukocyte antigens for IgAN and lupus nephritis, additionally highlighting anti-ETAR antibodies’ apparent connection with membranous nephropathy prognosis and anti-CXCR3 antibodies’ association with focal segmental glomerulosclerosis (FSGS) disease course.¹

“Glomerular diseases are autoimmunological disorders that involve many autoantibodies, and predicting the disease course is challenging,” Maciej Szymczak, MD, PhD, a nephrologist and internal medicine specialist at Wroclaw Medical University in Poland, and colleagues wrote.¹ “Furthermore, appropriate glomerular disease progression markers are still lacking.”

A prominent cause of renal impairment, glomerulonephritis leads to 10%-15% of end-stage renal disease cases in the United States and is the third most common cause behind diabetes mellitus and hypertension. Often, the disease becomes progressive without timely intervention and eventually leads to morbidity, underscoring the need for reliable prognostic markers.²

To assess the influence of anti-ETAR and anti-CXCR3 antibodies on the disease course of specific glomerulonephritis types, investigators conducted a prospective observational study of patients with histopathologically confirmed membranous nephropathy (n = 18); FSGS (n = 25); systemic lupus erythematosus (n = 17); IgAN (n = 14), mesangiocapillary glomerulonephritis (n = 6); anti-neutrophil cytoplasmic antibodies (c-ANCA) vasculitis (n = 40); and perinuclear anti-neutrophil cytoplasmic antibodies (p-ANCA) vasculitis (n = 16). Patients were compared with a control group of healthy Caucasian individuals without proteinuria; with a creatinine level no higher than 1.3 mg/dL; and without a history of kidney or autoimmunological diseases (n = 22).¹

Participants’ blood samples were collected simultaneously with blood collection for standard laboratory evaluation. Investigators assessed the serum concentrations of ETAR and CXCR3 antibodies with commercially available enzyme-linked immunosorbent assay (ELISA) kits. Clinical parameters including creatinine, total protein, and albumin serum levels were examined for 2 years after the initial basic evaluation to assess the correlation between clinical course markers and basic receptor antibody levels.¹

Investigators observed lower anti-ETAR antibody levels among patients with FSGS and IgAN than in the control group (P = .01 and P = .04, respectively). Additionally, they noted anti-ETAR antibody levels among patients with lupus nephritis were higher than those of the membranous nephropathy (P = .0001), FSGS (P = .0001), IgAN (P = .0001), and c-ANCA vasculitis (P = .002) groups.¹

In contrast, the basic anti-CXCR3 antibodies did not differ between the control group and specific glomerular diseases.¹

Further analysis revealed basic anti-ETAR levels in patients with membranous nephropathy and IgAN correlated positively with creatinine levels after 2 years of observation (both P = .03). Additionally, investigators noted basic anti-CXCR3 antibodies correlated with creatinine levels after 2 years in the IgA nephropathy group (P = .01).¹

In the systemic lupus erythematosus group, a negative association was observed between basic anti-ETAR antibodies and total protein levels after 3 months (P = .03) and with the albumin level after 3 (P = .01) and 6 months (P = .03) of observation. Similarly, anti-CXCR3 antibody levels were found to be negatively correlated with total protein levels after 2 years of observation (P = .03) and with the basic albumin level (P = .02) and albumin level after 1 month of observation (P = .04).¹

Results also showed anti-ETAR antibody levels correlated with anti-CXCR3 antibody levels in patients with lupus nephritis (P = .01) and IgAN (P = .001).¹

“This prospective observation showed that anti-ETAR and anti-CXCR 3 antibody levels are connected with the course of IgA nephropathy and lupus nephritis,” investigators concluded.¹ “An influence of ETAR antibodies on the course of membranous nephropathy, and CXCR3 antibodies on the course of FSGS, is also probable.”

References

1. ^{Szymczak M, Heidecke H, Żabińska M, et al. The Influence of Anti-ETAR and Anti-CXCR3 Antibody Levels on the Course of Specific Glomerulonephritis Types. Journal of Clinical Medicine. https://doi.org/10.3390/jcm13247752}
2. ^{Kazi AM, Hashmi MF. Glomerulonephritis. StatPearls [Internet]. June 26, 2023. Accessed January 20, 2025. https://www.ncbi.nlm.nih.gov/books/NBK560644/}