Background: Lung transplantation (LuT) stands as a final lifesaving measure in patients having many end-stage lung diseases including rapidly progressive interstitial lung disease (RP-ILD). RP-ILD, a subtype of anti-melanoma-differentiation-associated gene-5 antibody (MDA5) positive dermatomyositis (DM) associated ILD, is known to have progression and high mortality despite aggressive immunosuppressive therapies. The disappearance of MDA-5 antibody after LuT as a remission marker of amyopathic DM has been suggested. This study aims to evaluate the significance of anti-MDA5 antibody and related clinical conditions in LuT patients.
Methods: Twenty-two patients who received LuT at Samsung Medical Center (SMC) and 77 LuT patients registered in Korean Organ Transplantation Registry (KOTRY) were included. Total 194 paired sera before and after LuT were subjected to anti-MDA5 antibody measurement either using Luminex bead array or ELISA The cut-offs defining the positive results were mean fluorescence intensity (MFI) 3,870 and 100 U/mL, respectively. The collection time for post-transplant sera varies from one year to three years after LuT. The results of anti-MDA5 antibody were analyzed including the clinical information of the enrolled patients.
Results: The pre-transplant anti-MDA5 antibody values of six ILD patients including four RP-ILD measured using luminex microarray were significantly higher than those of non-ILD patients (MFI median 9,657.7, range 1,067-24,188 vs. median 791.5, range 237.1-736.2, respectively, P-value  0.0012). The results of six sera including three RP-ILD patient’s sera were over cut off value. The post-transplant anti-MDA-5 antibody levels were markedly reduced in all LuT patients, particularly in ILD patients (MFI median 1,282.6, range 163.1-4252.6). Among the sera of 24 ILD patients from KOTRY, only the pre-transplant sera of five RP-ILD patients showed significantly elevated levels of anti-MDA5 antibodies (median level of 148.0 U/mL, range 105.3-179.0). At one year after LuT, anti-MDA5 antibody levels were lowered to median 9.9 U/mL (range 3.2-36.2). In 8 RP-ILD patients from both cohort, none of them had evidences of ILD recurrence at one to three year after LuT.
Conclusions: The level of anti-MDA5 antibody was elevated in most RP-ILD patients before lung transplantation. However, the level of anti-MDA5 antibody dramatically reduced and remained at a low level without the evidences of clinical presentation after transplantation. This finding suggests that serial monitoring of anti-MDA5 antibody might be beneficial to predict the recurrence of RP-ILD after lung transplantation.