Background/Purpose: Patients with lupus nephritis (LN) achieve variable clinical response following Rituximab (RTX) based B-cell depletion therapy, with rituximab treatment aiming to decrease the use of cyclophosphamide rescue therapy. In LN, the presence of interstitial B cells is known to be associated with renal dysfunction and active lesions. However, data on renal B-cell depletion and the clinical response to RTX in LN is limited. Therefore, we investigated the relationship between B-cell depletion in peripheral blood and the kidney, and clinical response to RTX in LN.

Methods: Six patients with LN (2 male, 4 female) had a renal biopsy performed following treatment with RTX (2 x 1g, a week apart) for on-going disease activity. Patients underwent a renal biopsy for the following reasons: decline in renal function (n=4) and nephrotic syndrome (n=2). 5 of the 6 patients had a previous renal biopsy, with 3/5 of the patients having a preceding renal biopsy in the year (between 5-8 months) prior to rituximab therapy. B-cell depletion in peripheral blood was assessed by measurement of CD19+ cells by flow cytometry. Renal B-cells were investigated using immunohistochemistry (IHC) on formalin-fixed paraffin-embedded sections using 2 different monoclonal antibodies against 2 different B-cell markers: anti-PAX-5 and anti-CD79.

Results: Patient characteristics including treatment prior to renal biopsy, serum creatinine, urine protein-creatinine ratio (PCR) and the histological type of LN are shown in Table 1. The patients had renal biopsies a median of 3 months (range 0.5 to 5 months) following rituximab. Anti-CD79 immunohistochemistry Five of six patients had detectable interstitial B cells with anti-CD79 staining. These patients had: (i) progressive chronic kidney disease, (ii) required 3 months of dialysis and subsequently recovered renal function but had progressive CKD and 6 years post-biopsy is approaching end-stage renal disease (ESRD) (iii) commenced peritoneal dialysis within 6 months of the renal biopsy. (iv) stable chronic kidney disease (CKD) (v) had predominantly sclerosed glomeruli with little B-cell staining and subsequently did not recover renal function and remained dialysis dependent. The 6^th patient without detectable staining had a Class V LN with normal renal function at follow-up in complete disease remission. Anti Pax-5 immunohistochemistry Immunohistochemistry with anti-Pax-5 showed similar staining patterns to that with anti-CD79 in 4 patients. The 2 patients without detectable staining with anti-Pax-5 had Class V (patient 2) and Class VI (patient 4), Therefore staining was only present in proliferative glomerular lesions. Peripheral B-cells Four patients had less than 0.002 x 10⁹ CD19+ cells/L; 1 patient CD19 0.042 x 10⁹ cells/L and 1 patient with a Class V and with no detectable B cell infiltration, had a CD19 count of 0.03 x 10⁹ cells/L at the time of renal biopsy.

Conclusion: This retrospective study demonstrates clinically relevant discrepancy in B-cell depletion between peripheral blood and the kidney in patients with LN with the persistence of interstitial B-cells suggesting resistance to rituximab-induced B-cell depletion and on-going renal inflammation. This, was associated with progressive CKD and end-stage renal failure in four patients whereas the patient with preserved renal function had no detectable B cells in the kidney. Therefore, we consider that improving B-cell depletion in the kidney may enhance clinical response to B-cell depletion therapy in lupus nephritis. Table 1. Renal biopsy data and parameters before and after rituximab.

CS-corticosteroids; CYC, cyclophosphamide; MMF, mycophenolate mofetil; Aza, Azathioprine;

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/discrepancy-in-rituximab-induced-b-cell-depletion-in-peripheral-blood-and-the-kidney-and-relationship-with-clinical-response-in-patients-with-lupus-nephritis/