Plasma Cell-Rich Acute Rejection in a Young Kidney Transplant Patient and the Role of anti-CD38 Therapy

Plasma cell-rich acute rejection (PCAR) is a rare form of kidney allograft rejection characterized by prominent interstitial plasma cell infiltration. It is associated with poor graft outcomes, and its optimal management remains undefined. We report the case of a young patient with PCAR treated with daratumumab, resulting in significant histological improvement.

A 21-year-old Black woman received a deceased-donor kidney transplant at the age of 16 for end-stage kidney disease secondary to Alport syndrome, with subsequent normalization of graft function (creatinine 0.9 mg/dL). The maintenance immunosuppressive regimen consisted of cyclosporine, mycophenolate mofetil, and corticosteroids.

Five years later, she developed acute kidney injury (creatinine 2.8 mg/dL), accompanied by sub-nephrotic proteinuria (1.5 g/24h), and microhematuria. Cyclosporine levels were within target. Donor-specific antibodies (DSA) were positive (DR52, MFI 15240; DQ4, MFI 8452; DP3, MFI 1442). Kidney biopsy revealed mixed rejection (Banff score: g1, ptc2, C4d not available, cg0, i3, t2, v1) with a plasma cell-rich interstitial infiltrate (60–70% of the total infiltrate), consistent with PCAR. Immunohistochemistry was negative for monoclonality and IgG4 expression. Treatment included methylprednisolone pulses and four weekly doses of daratumumab — the first administered intravenously (16 mg/kg) and the subsequent three subcutaneously (1800 mg). Cyclosporine was replaced by tacrolimus (target trough 6–8 ng/mL). The therapy was well tolerated, improving kidney function (creatinine 1.3 mg/dL) and lower DSA levels (DR52, MFI 5000; DQ4, MFI 1500; DP3 MFI <1000). After one month, kidney biopsy showed improvement in histological lesions (Banff score: i1, t1, v0, g0, ptc2, C4d1, cg0) and marked reduction of the plasma cell infiltrate (Figure 1). Given the poor prognosis of PCAR, treatment was further intensified with five plasmapheresis sessions, anti-thymocyte globulin (total dose 6 mg/kg) and high-dose intravenous immunoglobulin, achieving stable graft function.

PCAR is a poorly understood rejection phenotype typically associated with high rates of graft loss. It may occur in the context of antibody-mediated rejection (AMR), T cell-mediated rejection, or mixed rejection, with or without detectable DSA(1). Treatment strategies are not standardized and vary according to the clinical and histological context. In this setting, the anti-CD38 monoclonal antibody daratumumab may serve as a valuable adjunct to standard-of-care therapy. Beyond its ability to deplete plasma cells and reduce DSA production, daratumumab may also modulate natural killer cell activity, thereby mitigating antibody-independent microvascular injury. It is generally well tolerated, with a favorable safety profile and the practical advantage of subcutaneous administration, reducing hospitalization needs. However, questions remain regarding optimal dosing schedules and duration of therapy. In the absence of robust evidence, protocol biopsies may be useful to assess histologic response and guide treatment adjustments.

PCAR is a rare and severe rejection with no standardized management. Our experience suggests that daratumumab may offer a promising therapeutic option to reduce plasma cell infiltration and improve graft outcomes. Further studies are needed to confirm its efficacy and define optimal protocols.