Anti-Myeloperoxidase Antibodies Associate with Future Proliferative Lupus Nephritis

Area of Science:

• Nephrology
• Immunology
• Autoimmune Diseases

Background:

• The subclinical pathophysiology of proliferative lupus nephritis (PLN) remains unclear.
• Myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA) is linked to PLN, but its prediagnostic levels are unknown.

Purpose of the Study:

• To investigate prediagnostic MPO-ANCA levels in patients who later develop PLN.
• To compare MPO-ANCA levels in PLN patients with those in healthy individuals and patients with SLE without LN.
• To examine the temporal relationship between MPO-ANCA and anti-double stranded DNA antibodies (dsDNAab) in PLN development.

Main Methods:

• Retrospective case-control study using the Department of Defense Serum Repository (DoDSR).
• Compared prediagnostic MPO-ANCA levels in 23 biopsy-confirmed PLN patients against age-, sex-, and race-matched controls (healthy and SLE without LN).
• Analyzed the timing of MPO-ANCA and dsDNAab detection relative to PLN diagnosis.

Main Results:

• A significantly higher proportion of PLN patients had elevated prediagnostic MPO-ANCA levels (≥3 U/mL and ≥6 U/mL) compared to controls (91% vs. 43%, p < 0.001; 57% vs. 5%, p < 0.001).
• Elevated MPO-ANCA levels (≥3 U/mL) were significant up to 1-4 years before diagnosis (<1 year: 88% vs. 39%, p = 0.007; 1-4 years: 87% vs. 38%, p = 0.009).
• Statistically significant subclinical MPO-ANCA levels preceded significant subclinical dsDNAab levels (89% vs. 11%, p = 0.003).

Conclusions:

• Prediagnostic MPO-ANCA levels can differentiate future PLN from SLE without LN.
• MPO-ANCA emerges before clinical disease and subclinical dsDNAab, suggesting a potential direct role in PLN pathogenesis.