Антитела к подоцину и KIRREL1 предсказывают тяжелое течение болезни и отказ почек

Antipodocin and anti-KIRREL1 autoantibodies delineated a high-risk autoimmune podocytopathy phenotype characterized by focal segmental glomerulosclerosis (FSGS), steroid resistance, chronic kidney disease (CKD) progression, and frequent post-transplant recurrence, according to a study published in the Journal of the American Society of Nephrology. In contrast, isolated antinephrin antibodies defined a steroid-sensitive minimal change disease course with preserved kidney function. In this multicenter analysis of 471 samples, investigators integrated serologic testing with super-resolution microscopy across 213 cases and 258 controls. The cohort included 146 kidney biopsies (minimal change disease, n = 63; FSGS, n = 83) and 128 sera, with 61 paired specimens enabling assay comparison. Anti-slit diaphragm antibodies were identified in 67 of 213 patients (32%), with antinephrin predominating (63%), followed by antipodocin (9%), anti-KIRREL1 (3%), and multiantigen reactivity (25%). Super-resolution stimulated emission depletion microscopy localized IgG deposits to slit diaphragm proteins, demonstrating colocalization with nephrin, podocin, or KIRREL1 in 35 of 48 evaluable biopsies. Distinct antigenic patterns were observed in 44% of minimal change and 24% of FSGS biopsies. Notably, 37% of IgG-positive cases exhibited multiantigen targeting, consistent with intermolecular epitope spreading. ELISA assays showed high specificity (98%-99%) but reduced sensitivity relative to tissue-based detection, with area under the curve values of 0.81 for podocin, 0.84 for KIRREL1, and 0.87 for nephrin. Clinical phenotypes diverged sharply by antibody specificity. Isolated antinephrin antibodies were strongly associated with minimal change disease (91%) and steroid responsiveness (88%), with no CKD or kidney failure observed over 120 months. In contrast, antipodocin and/or anti-KIRREL1 antibodies were linked to FSGS lesions in 84% of cases compared with 10% among antinephrin-only patients (P <.001), along with a higher glomerulosclerosis burden. Therapeutic response also differed significantly. Steroid resistance occurred in 58% of patients with antipodocin or anti-KIRREL1 antibodies vs 12% with antinephrin alone (P <.001), and second-line immunosuppression was more frequently required (96% vs 64%; P =.005). Baseline estimated glomerular filtration rate was lower in the high-risk group (80.7 vs 120 mL/min/1.73 m²; P =.03). Long-term outcomes underscored prognostic separation. CKD developed in 36% of patients with antipodocin or anti-KIRREL1 antibodies, and kidney failure occurred in 24% (P =.002), with progressive risk evident through 72 months. No patient with isolated antinephrin antibodies developed CKD or kidney failure. Among 26 transplant recipients with FSGS, recurrence occurred in 83% of antibody-positive patients vs 5% of others, implicating these autoantibodies in post-transplant disease reactivation. “[D]etection of antipodocin or anti-KIRREL1 antibodies informs about chronic course, poor prognosis and potential recurrence after kidney transplantation in patients with autoimmune podocytopathies,” stated the authors. “Anti-nephrin-, podocin-, and KIRREL1-specific serology and/or high-resolution microscopy on the kidney biopsy should be included in diagnostic workup of patients with nephrotic syndrome and isolated proteinuria, enabling identification of immunologic subtypes that cannot be distinguished morphologically.” This article originally appeared on Rare Disease Advisor References: Raglianti V, Angelotti ML, Cirillo L, et al. Anti-podocin and anti-KIRREL1 antibodies and steroid resistance, FSGS, and disease recurrence after transplantation in autoimmune podocytopathies. J Am Soc Nephrol. Published online July 23, 2026. doi:10.1681/ASN.0000001195