Clarifying the immunoglobulin light chain variable gene usage in Chinese patients with renal AL amyloidosis.

BACKGROUND The association between immunoglobulin light chain variable (IGVL) gene usage and clinicopathological features in renal AL amyloidosis requires further research. This study analyzed IGVL genes and their associations with clinicopathological characteristics, organ involvement and survival outcomes in a Chinese cohort.

METHODS We retrospectively enrolled 273 renal AL amyloidosis patients. Amyloid deposits were microdissected and subjected to mass spectrometry (MS)-based proteomics to identify IGVL genes. Clinicopathological features, organ involvement and survival data were systematically analyzed.

RESULTS IGVL genes were successfully identified in 250 patients (92%). IGLV6-57 (32%) was predominant, IGKV1 family (12%) was the most prevalent in AL-κ cases. IGLV6-57 was associated with a higher rate of full nephrotic syndrome, while was linked to milder vascular amyloid deposition and total amyloid deposition. IGKV1 was associated with heavier amyloid burden, severe interstitial inflammation and a higher rate of hepatic involvement, IGLV6-57 was correlated with reduced hepatic involvement. IGLV1-51 potentially predicted rapid renal progression and dialysis risk.

CONCLUSION The IGVL gene usage is associated with distinct clinicopathological features in renal AL amyloidosis, IGLV6-57 is linked to a higher frequency of full nephrotic syndrome, IGKV1 is associated with severe kidney structural damage and hepatic tropism, and IGLV1-51 potentially predicts poor renal survival.