Association between interstitial fibrosis/tubular atrophy (IFTA) on kidney biopsies and anti Ro60 antibody positivity in patients with lupus nephritis (LN)

Abstract

Background

Interstitial fibrosis and tubular atrophy (IFTA) are key predictors of renal outcomes in lupus nephritis (LN), but serologic markers that identify patients at higher risk for tubulointerstitial damage are poorly defined. Anti-Ro60 antibodies are associated with heightened systemic immune activation and worse renal outcomes in systemic lupus erythematosus, but their relationship to IFTA in LN is unknown.

Methods

We performed a retrospective cohort study of adults with biopsy-confirmed LN at a single academic center. Clinical data, autoantibody profiles, and renal histopathology were abstracted from the medical record at or near the time of kidney biopsy. Ro60 status was determined by standard clinical immunoassays. IFTA severity was graded by a renal pathologist as none, mild, moderate, or severe. Ordinal logistic regression was used to evaluate the association between Ro60 positivity and IFTA severity. A multivariable proportional odds model included Ro60 positivity (primary exposure), Black race (the only variable with p < 0.05 in the univariable analysis), and ISN/RPS class IV LN (an a priori clinical risk factor for fibrosis). Sensitivity analyses included dichotomizing IFTA (absent/mild vs moderate/severe), excluding the single severe IFTA case, and restricting to Black patients.

Results

Forty-one patients met the inclusion criteria; 16 (39%) were Ro60-positive, and 25 (61%) were Ro60-negative. Ro60-positive patients were more often Black and had lower C3 and C4 levels; the distribution of LN classes was similar between groups. In univariable analysis, Ro60 positivity was associated with higher odds of more severe IFTA (OR 3.05; 95% CI 0.86–11.5; p = 0.087), while Black race was strongly associated with worse IFTA (OR 7.82; 95% CI 1.02–93.12; p = 0.014). In the multivariable model limited to 29 complete cases, Ro60 positivity remained associated with higher IFTA severity (OR 2.76; 95% CI 0.77–13.04; p = 0.127), and Black race remained the strongest predictor (OR 8.06; 95% CI 0.92–275.61; p = 0.015); class IV LN was not significantly associated with IFTA (OR 1.90; 95% CI 0.37–13.24; p = 0.371). In a sensitivity analysis excluding the single patient with severe IFTA, the association between Ro60 positivity and IFTA strengthened (OR 5.25; p = 0.028), and Black race remained strongly associated with worse IFTA (OR 15.79; p = 0.005).

Conclusions

In this biopsy-based LN cohort, Ro60 positivity was associated with a consistent trend toward more severe IFTA, with a statistically significant association in sensitivity analysis excluding one severe outlier case. Black race was the most robust predictor of IFTA severity, highlighting persistent racial disparities in LN-related kidney damage. These findings support the hypothesis that anti-Ro60 antibodies contribute to tubulointerstitial injury and suggest that Ro60 status may help identify LN patients at higher risk for chronic structural damage. Larger, prospective studies are needed to confirm these associations and clarify the prognostic role of Ro60 in LN.