Background: Alemtuzumab induction (AZI) can be used for early steroid withdrawal in kidney transplant (KTx) recipients. There is evidence that AZI-induced lymphocyte depletion leads to increased transitional B cells and dominance of naïve B cells. In this study we characterize the clinicopathologic features of acute rejection after AZI.

Methods: Inclusion criteria were: 1) KTx from 1/2005 to 10/2016 who received AZI and 2) biopsy-proven acute cellular rejection (ACR), borderline ACR, and/or acute antibody mediated rejection (AAMR) within 2.5 years after KTx. Slides were reviewed and classified by Banff criteria. CD138+ plasma cells were counted on immunoperoxidase stained sections in five 40x fields (hpf) in the most concentrated areas.

Results: Of 370 KTx recipients who received AZI, 25 (6.8%) had an acute rejection episode at a mean of 9.1 months post-transplant (range 0.2-26.6). The average age was 48 years (range 19-64); 72% were men. The donors were 88% living and 12% deceased. The most common etiologies for ESRD were polycystic kidney disease (32%) and IgA nephropathy (25%). 56.5% were protocol biopsies and 43.5% were indicated for elevated creatinine (SCr). The mean SCr was 2.2 mg/dL (range 1.0-6.1) at biopsy. 22 patients had ACR or borderline ACR and 3 patients had AAMR. 4 (16%) had endothelialitis. All 3 AAMR cases were diffusely C4d+. 73% (16/22) of patients with ACR or borderline ACR showed a plasma cell rich pattern. The mean CD138 positive plasma cell count overall was 37 cells/hpf (range 1-124), including 51/hpf (range 3-124) for ACR and 27/hpf (range 1-78) for borderline ACR.

Patients with ACR or borderline ACR were treated with bolus steroids (82%) or anti-thymocyte globulin (18%). Of the 20 patients with ACR or borderline ACR with elevated SCr, 6 (30%) had decreased SCr of at least 0.2 mg/dL 1 month later. The mean SCr was 1.7 mg/dL (range 0.9-4.7) at 1 month and 1.6 mg/dL (1.1-2.8) at 1 year after acute rejection. The mean follow-up time was 5.0 years (range 0.1 to 12.0) post-transplant.

Conclusion: KTx recipients who received AZI tend to show a different rejection phenotype, plasma cell-rich acute cellular rejection. This unique phenotype may be due to a different B cell repertoire that develops after AZI, and thus potentially has a different response to conventional anti-rejection therapy.

CITATION INFORMATION: Zhang P, Amer H, Schinstock C, Alexander M, Cosio F, Stegall M, Cornell L. Clinical and Pathologic Characteristics of Acute Rejection After Alemtuzumab Induction in Kidney Transplant Recipients. Am J Transplant. 2017;17 (suppl 3).

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