B- and T-cell subpopulations in patients with severe idiopathic membranous nephropathy may predict an early response to rituximab.
Primary membranous nephropathy (PMN) is characterized by antibodies to the podocyte, but little is known about B- and T-cell populations and their response to rituximab is controversial. To help resolve this we compared 33 lymphocyte subpopulations and 27 cytokines/chemokines in 25 patients with severe PMN and 27 age-matched healthy individuals. At baseline, patients had a significantly increased percentage of naive B-cells with significantly decreased switched and non-switched memory B-cells. There was a significantly decreased percentage of natural killer (NK) cells with an increase in the CD56brightCD16-/loNK subset. There were a significantly decreased percentage of regulatory T cells, together with an increased plasma concentration of TNF-alpha, IL-5 and IL-2RA. We then investigated 16 patients at eight days and three and six months after treatment with rituximab added to supportive therapy compared to nine patients with supportive therapy alone. After rituximab, B-cell recovery was still incomplete at six months, with persistent alterations of B-cell subsets, a significant increase of both T-regulatory (Treg) cells and NK cells, and a significant decrease of both the CD56brightCD16-/loNK subset and TNF-alpha levels. The patients who clinically responded to rituximab had a significantly lower percentage of Tregs at baseline compared to non-responders and a significantly increased percentage at day eight. Tregs remained unchanged in non-responders and in patients treated with supportive therapy alone. Thus, evaluation of Tregs might be useful for predicting early response to rituximab.
AP-HP, Hôpital Pitié-Salpêtrière, Biotherapy (CIC-BTi) and Inflammation-Immunopathology-Biotherapy Department, Paris, France; Sorbonne Universités, UPMC Univ Paris, Paris, France; INSERM, UMR_S 959, Paris, France.
Michelle
M
Rosenzwajg
Sorbonne Universités, UPMC Univ Paris, Paris, France; INSERM, UMR_S 1155, Paris, France.
Eva
E
Languille
Sorbonne Universités, UPMC Univ Paris, Paris, France; INSERM, UMR_S 1155, Paris, France.
Hanna
H
Debiec
AP-HP, Hôpital Pitié-Salpêtrière, Biotherapy (CIC-BTi) and Inflammation-Immunopathology-Biotherapy Department, Paris, France.
Joana
J
Hygino
AP-HP, Hôpital Tenon, Department of Nephrology and Dialysis, Paris, France.
Karine
K
Dahan
AP-HP, Hôpital Saint-Antoine, Department of Clinical Pharmacology and Unité de Recherche Clinique, Paris, France.
Tabassome
T
Simon
AP-HP, Hôpital Pitié-Salpêtrière, Biotherapy (CIC-BTi) and Inflammation-Immunopathology-Biotherapy Department, Paris, France; Sorbonne Universités, UPMC Univ Paris, Paris, France; INSERM, UMR_S 959, Paris, France.
David
D
Klatzmann
Sorbonne Universités, UPMC Univ Paris, Paris, France; INSERM, UMR_S 1155, Paris, France; AP-HP, Hôpital Tenon, Department of Nephrology and Dialysis, Paris, France. Electronic address: pierre.ronco@upmc.fr.
Pierre
P
Ronco
D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000097:blood; D016175:B-Lymphocyte Subsets / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D015415:Biomarkers / Q000097:blood; D018791:CD4 Lymphocyte Count; D019002:CD56 Antigen / Q000097:blood; D005260:Female; D058851:GPI-Linked Proteins / Q000097:blood; D015433:Glomerulonephritis, Membranous / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D016130:Immunophenotyping; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D053645:Interleukin-2 Receptor alpha Subunit / Q000097:blood; D015848:Interleukin-5 / Q000097:blood; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010297:Paris; D010641:Phenotype; D011237:Predictive Value of Tests; D017452:Receptors, IgG / Q000097:blood; D000069283:Rituximab / Q000009:adverse effects / Q000627:therapeutic use*; D012720:Severity of Illness Index; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D013997:Time Factors; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D001323:Autoantibodies; D015415:Biomarkers; D019002:CD56 Antigen; C428200:FCGR3B protein, human; D058851:GPI-Linked Proteins; C508017:IL2RA protein, human; C508599:IL5 protein, human; D007166:Immunosuppressive Agents; D053645:Interleukin-2 Receptor alpha Subunit; D015848:Interleukin-5; C522918:NCAM1 protein, human; D017452:Receptors, IgG; D014409:Tumor Necrosis Factor-alpha; D000069283:Rituximab
TNF-α; membranous nephropathy; memory B cells; natural killer cells; regulatory T cells; rituximab