Persistence of immunoglobulin-producing cells in parotid salivary glands of patients with primary Sjogren's syndrome after B cell depletion therapy

Autor: Rodney P. E. Pollard, Frans G. M. Kroese, Erlin A. Haacke, Saravanan Yuvaraj, Fred K. L. Spijkervet, Annie Visser, Cees G. M. Kallenberg, Nicolaas A. Bos, Arjan Vissink, Nishath Hamza, Hendrika Bootsma
Přispěvatelé: Guided Treatment in Optimal Selected Cancer Patients (GUTS), Personalized Healthcare Technology (PHT), Translational Immunology Groningen (TRIGR)
Jazyk: angličtina
Rok vydání: 2012
Předmět:
Pathology
medicine.medical_treatment
Antibodies
Monoclonal
Murine-Derived

DOUBLE-BLIND
Immunology and Allergy
Parotid Gland
SYSTEMIC-LUPUS-ERYTHEMATOSUS
B-Lymphocytes
biology
medicine.diagnostic_test
Middle Aged
Isotype
medicine.anatomical_structure
Lymphatic system
Sjogren's Syndrome
PLASMA-CELLS
Rituximab
Female
Antibody
medicine.drug
Adult
medicine.medical_specialty
Adolescent
BONE-MARROW
Immunology
General Biochemistry
Genetics and Molecular Biology

Lymphocyte Depletion
Young Adult
Rheumatology
stomatognathic system
Biopsy
medicine
Humans
Immunologic Factors
IMMUNOTHERAPY
Antibody-Producing Cells
IGA
Aged
business.industry
MEMORY
RITUXIMAB TREATMENT
Immunotherapy
Clone Cells
Immunoglobulin A
stomatognathic diseases
LYMPHOID-TISSUE
Immunoglobulin class switching
Immunoglobulin G
biology.protein
Bone marrow
business
FOLLOW-UP
Zdroj: Annals of the Rheumatic Diseases, 71(11), 1881-1887. BMJ PUBLISHING GROUP
ISSN: 0003-4967
Popis: ObjectivesTo assess the persistence of immunoglobulin-producing cell populations in the parotid salivary glands of patients with primary Sjögren's syndrome (pSS) after B cell depletion therapy with rituximab.MethodsThirteen patients with pSS and four control patients were included in this study. Patients with pSS were treated with rituximab or placebo. Sequence analysis was carried out on IgA- and IgG-encoding transcripts extracted from parotid salivary gland biopsy specimens taken before treatment and at 12–16 and 36–52 weeks after treatment.ResultsAt baseline, many clonally related sequences were seen in patients with pSS. The number of clonal expansions was significantly higher in patients with pSS than in control patients. Clonal expansions were composed of IgA- and/or IgG-expressing cells. Rituximab did not significantly alter the degree of clonal expansions. Groups of clonally related cells had members which were shared between biopsy specimens taken before and after treatment. Mutation frequencies of immunoglobulin sequences from clonally related cells in patients with pSS were higher after treatment.ConclusionsRituximab treatment does not alter the characteristic features of increased clonal expansions seen in the parotid salivary glands of patients with pSS. The presence of clonally related immunoglobulin-producing cells before and after rituximab treatment strongly suggests that immunoglobulin-producing cells persist in salivary glands of patients with pSS despite B cell depletion. The presence of mixed isotype expression within groups of clonally related cells indicates local class switching in salivary glands of patients with pSS. Persistent immunoglobulin-producing cells may underlie disease relapse after treatment.
Databáze: OpenAIRE