We have identified two important clinical implications. Cadaveric single-LTx for ESLD secondary to iMCD can be a possible therapeutic option, and TCZ can alleviate iMCD, ensuring a stable perioperative period during and after LTx.
First, LTx is an acceptable therapeutic option for patients with iMCD and ESLD. It is generally challenging to determine an indication for LTx for the treatment of ESLD secondary to iMCD due to its characterization as a systemic disease with possible multiple organ involvement. Although lung involvement in iMCD is common, to the best of our knowledge, there have been only two reports of LTx for the treatment of ESLD secondary to iMCD [4, 5]. One of the reports with 6 month follow-up showed that single-LTx can be feasible if the clinical manifestations of iMCD, except for the lungs, are controlled [5]. In our case, in an iMCD patient with bilateral lung involvement, single-LTx was an effective treatment without any complications in the residual native lung with a follow-up period of 32 months. However, since iMCD may recur with cessation of TCZ, lifelong administration of TCZ may be necessary to protect the allograft lung and control iMCD disease activity after transplantation, regardless of the procedure of single- or bilateral-LTx [8].
Second, TCZ, in addition to standard immunosuppressive therapy using a triple-drug regimen (tacrolimus, mycophenolate mofetil, and PSL), has been useful for iMCD during and after LTx. In this case, the IL-6 level was maintained at a low level (< 100 pg/mL), even with a temporal cessation of TCZ for 28 days after LTx. Glucocorticoid use following LTx suppresses hypercytokinemia and alleviates symptoms [2], and tacrolimus prevents iMCD from worsening by suppressing inflammation of T-helper 1 cells, which is considered a pathogenesis of iMCD [9]. Furthermore, the patient experienced no apparent rejection or development of DSA during the observation period. IL-6, a major cytokine involved in the transition of B cells to IgG-secreting plasma cells and finally to plasmacytoid cells, also stimulates Th17 cells which cause inflammation and graft rejection. Recent studies suggest that TCZ inhibits antibody production and suppresses inflammation by targeting the IL-6/IL-6R pathway [10, 11]. In the field of renal transplantation, it has been reported that patients with chronic antibody-mediated rejection who failed other therapies were treated with TCZ and had a significant decrease in DSA and stable renal function after 2 years [12, 13]. Thus, TCZ can reduce the risk of chronic antibody-mediated rejection after LTx.
Notably, in this case, the serum CRP level was not significantly elevated in the perioperative period. Although CRP levels are usually elevated even in patients without signs of sepsis and who are on immunosuppressive drugs [14], suppression of CRP in patients treated with TCZ can delay the diagnosis of serious infections [15]. It should be noted that CRP levels can be elevated in the perioperative period in lung transplant patients receiving TCZ. PCT, which is a marker of bacterial infection produced by a pathway independent of IL-6, has been proposed as a preferred surrogate marker of bacterial infection during TCZ treatment [16].
