Mizoribine reduces serum KL-6 levels in ANCA-associated vasculitis

Abstract

Interstitial pneumonitis is one of the life-threatening diseases associated with ANCA-associated vasculitis. The measurement of serum levels of KL-6, which is a MUC1 mucin and is expressed on type II alveolar pneumocytes and bronchial epithelial cells [1], may be a good monitoring system for the diagnosis and follow-up of interstitial pneumonitis in ANCA-associated vasculitis patients [2]. Moreover, elevated serum KL-6 levels were reduced during convalescence induced by glucocorticoid therapy [2]. In the present case, the elevated serum KL-6 level was preserved during glucocorticoid therapy, but decreased to within the normal range with additional treatment by mizoribine (MZR).A 65-year-old woman visited our hospital complaining of a dry cough and low-grade fever. Crepitate sounds were heard in her chest, and chest X-rays and computed tomography showed interstitial pneumonitis in both lower lung fields. On urinalysis, mild proteinuria (urinary excretion of protein, 0.5 g/day), hematuria, and cellular casts were revealed. Mild anemia (hemoglobin concentration, 11.5 g/dl) and leukocytosis (11,000/mm 3 ) were observed. Although her serum creatinine level (0.66 mg/dl) was within the normal range, her serum cystatin C level was elevated to 0.87 mg/l. Serology revealed elevated levels of C-reactive protein (8.04 mg/dl), MPO-ANCA (208.5 U/ml), and KL-6 (526 U/ml). The major histological finding of renal biopsy was focal necrotizing glomerulonephritis without deposition of immunoglobulins or complements. She was diagnosed with MPO-ANCAassociated vasculitis and treated with an oral corticosteroid (prednisolone 30 mg/day). Although serum C-reactive protein was promptly normalized and MPO-ANCA titers gradually decreased, her high level of serum KL-6 was preserved (Fig. 1). Moreover, her HbA1c level was elevated to 7.0%, and she had been treated with nateglinide. Eighteen months after the initiation of glucocorticoid therapy, the dose of prednisolone was reduced to 7.5 mg/ day and MZR was additionally started at a dosage of 150 mg once a day. At the start of MZR administration, no new symptoms of vasculitis or signs of relapse were noted, and ANCA titers were preserved within the normal range (below 9.0 U/ml). In the 6 months after the initiation of MZR therapy, her elevated serum KL-6 level gradually fell to within the normal range (below 500 U/ml). Although the extent of interstitial pneumonitis in both lower lung fields on chest X-rays and computed tomography was not changed after KL-6 was decreased to the normal range, that area was not expanded.MZR has an immunosuppressive effect equivalent to that of azathioprine, but shows lower hepatic toxicity and myelosuppression. MZR is useful for preemptive treatment of ANCA-associated renal vasculitis patients with a high risk of relapse [3]. MZR caused the delay in the histological development of peribronchial and perivascular lymphocytic infiltrations in the lungs of MRL/lpr/lpr mice [4]. MZR improved renal tubulointerstitial fibrosis in a rat model of unilateral ureteral obst...

Monitoring with serum SP-A, SP-D, and KL-6 in a patient with interstitial pneumonia complicated with ANCA-associated glomerulonephritis

“…In patients with ANCA-associated vasculitis, Iwata et al [12] reported that the measurement of serum KL-6 levels may be a good monitoring system for the diagnosis and follow-up of IP. However, there are few reports on the simultaneous monitoring with serum SP-A, SP-D and KL-6 in patients with ANCA-associated IP [13].…”

KL-6 in ANCA-Associated Vasculitis Patients with and without ILD: A Machine Learning Approach

“…Some authors have reported higher serum concentrations of KL-6 in AAV patients with ILD than in those without lung involvement, suggesting that this mucin could be a useful prognostic marker [ 18 , 19 , 20 ]. However, these few studies were conducted in small cohorts and did not consider disease activity or extrapulmonary manifestations.…”

“…Different reports have demonstrated elevated serum KL-6 concentrations in various ILDs, including connective tissue disorders associated with ILD [14][15][16][17], suggesting that this marker is not only useful for diagnosis but also for prognosis and for monitoring response to therapy. Some authors have reported higher serum concentrations of KL-6 in AAV patients with ILD than in those without lung involvement, suggesting that this mucin could be a useful prognostic marker [18][19][20]. However, these few studies were conducted in small cohorts and did not consider disease activity or extrapulmonary manifestations.…”