Anti-Ro52 Autoantibodies Are Related to Chronic Graft-vs.-Host Disease After Allogeneic Hematopoietic Stem Cell Transplantation

Abstract

Chronic graft-vs.-host disease (cGVHD) remains a major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Previous studies have shown that autoantibodies play an important role in the development of cGVHD. Anti-nuclear autoantibodies (ANA) is the most frequently detected autoantibodies in patients with cGVHD, but the role of anti-Ro52 autoantibodies (anti-Ro52) in cGVHD remains largely unknown. In this study, we analyzed autoantibodies from 84 patients after allo-HSCT, including 42 with active cGVHD and 42 without cGVHD. Autoantibodies were found in 36 (42.9%) patients. Among these autoantibody-positive patients, 28 (77.8%) patients had active cGVHD. The most frequent autoantibodies in patients with active cGVHD were ANA (50.0%), anti-Ro52 (28.6%) and anti-mitochondrial autoantibodies type 2 (4.8%). We further explored the association between anti-Ro52 and cGVHD. Patients with active cGVHD had higher anti-Ro52 levels than patients without cGVHD (P < 0.05). The increases of anti-Ro52 levels were more significant in patients with moderate/severe cGVHD compared to those of patients without cGVHD (P < 0.05). Stratified and multivariable logistic regression analysis demonstrated that moderate/severe cGVHD was an independent risk factor for the levels of anti-Ro52 (P < 0.01). ROC analysis confirmed anti-Ro52 as a risk factor for progression of skin cGVHD. Moreover, the anti-Ro52 levels were highly correlated with the levels of B cell-activating factor (BAFF) and IgG1 antibodies. Our study demonstrates that anti-Ro52 is associated with cGVHD. The increased levels of anti-Ro52 were associated with higher levels of BAFF and IgG1 antibodies, suggesting a mechanistic link between elevated anti-Ro52 levels and aberrant B cell homeostasis.

Value of Autoantibody Expression During Long-Term Follow-Up in Paediatric ALL Patients After Allogeneic Haematopoietic Stem Cell Transplantation

“…While cGvHD patients had a higher frequency of antinuclear autoantibodies than did patients without cGvHD (88 vs. 79%, respectively; p = 0.07), this difference did not reach statistical significance. This is in contrast to findings by Patriarca et al ( 20 ) and Yang et al ( 21 ) in adult HSCT patients and might possibly be explained by the lower incidence of cGvHD in paediatric patients. Further analyses regarding organ involvement of cGvHD and autoantibody profiles in our cohort were hampered by the low case numbers.…”

“…In this homogenous study cohort, we detected autoantibodies in 65% of patients, higher than in recently published adult cohorts ( 18 , 21 ). When comparing demographic data and transplant characteristics of patients with and without autoantibody expression there were no significant differences.…”

“…Chronic GvHD shares many similarities with de novo autoimmune disorders: presence of autoantibodies leads to target tissue damage, immune complex formation, and tissue deposition ( 15 ). An association between cGvHD and autoantibody expression has been described ( 18 – 21 ). Indeed, autoantibodies may be detectable before the onset of clinical manifestation of cGvHD ( 15 ).…”

TRIM21/Ro52 - Roles in Innate Immunity and Autoimmune Disease

“…Studies of patients undergoing hematopoietic stem cell transplantation suggest a link between elevated BAFF expression and anti-TRIM21 autoantibodies (169). Increased BAFF may support the survival of TRIM21-targeting autoreactive memory B cells.…”

“…Higher anti-TRIM21 autoantibody titres in pSS are associated with greater localised and systemic disease manifestations including parotid enlargement, haematological abnormalities and central nervous system involvement ( 168 ). Studies of patients undergoing hematopoietic stem cell transplantation suggest a link between elevated BAFF expression and anti-TRIM21 autoantibodies ( 169 ). Increased BAFF may support the survival of TRIM21-targeting autoreactive memory B cells.…”