Background The IgG4-related disease is a systemic syndrome, which may involve virtually any organ or system. The most characteristic clinical-pathological presentation complaints are autoimmune pancreatitis type 1, the symmetrical swelling of the lacrimal, parotid and submandibular glands, the inflammatory pseudotumor, retro peritoneal fibrosis and involvement of lymph nodes. Lymphocytes and plasma cells tissue infiltrate, with a ratio IgG4+ / IgG+ cells > 40% and a peculiar tissue fibrosis, named storiform, are the pathologic characteristics of the disease. The purpose of the study was to evaluate the expression of B-lymphocyte stimulating factors BAFF (B-cell activating factor) and APRIL (a proliferation induced ligand), as well BAFF-Receptor, by immunohistochemistry of bioptic specimens of a case-series of patients with proved diagnosis. Methods Nine patients (age range 34-78 yrs) with mean IgG4 serum concentration 548 mg / dl (range 124-1520), 6 with sclerosing pancreatitis, 5 with lymphadenopathy, 4 with sialadenitis, 3 with inflammatory orbital pseudotumor, 2 with dacryoadenitis and 1 with prostate hypertrophy had been enrolled. Bioptic tissue samples have been evaluated by immunohistochemistry with anti-BAFF, anti-BAFF-R, anti-APRIL antibodies and semi-quantitative analysis was performed and Immuno Reactivity Score was used (IRS=% of positive cells x staining intensity). Results APRIL and BAFF were expressed at same level (IRS mean 60.6±40 and 67.5±55, respectively) in tissues biopsies. APRIL and BAFF were localized outside the germinal center, with a cytoplasmic staining. BAFF R (IRS mean 170.6±109) was positive in the lymphocytes agglomerates and inside the germinal centers. Moreover, IgG4 correlates with BAFF R IRS ( r=0.56), and do not correlate with APRIL and BAFF immune staining. Conclusions Our data reinforce the hypothesis of the major role played by B lymphocyte activation in this disease and suggest a possible therapeutical approach by monoclonal antibodies specific for B-lymphocytes activating factors.
BAFF (B-cell activating factor) expression in IgG4-related disease
VIGLINO, Francesco;BOITA, MONICA;HEFFLER, Enrico Marco;BUCCA, Caterina;ROLLA, Giovanni
2015-01-01
Abstract
Background The IgG4-related disease is a systemic syndrome, which may involve virtually any organ or system. The most characteristic clinical-pathological presentation complaints are autoimmune pancreatitis type 1, the symmetrical swelling of the lacrimal, parotid and submandibular glands, the inflammatory pseudotumor, retro peritoneal fibrosis and involvement of lymph nodes. Lymphocytes and plasma cells tissue infiltrate, with a ratio IgG4+ / IgG+ cells > 40% and a peculiar tissue fibrosis, named storiform, are the pathologic characteristics of the disease. The purpose of the study was to evaluate the expression of B-lymphocyte stimulating factors BAFF (B-cell activating factor) and APRIL (a proliferation induced ligand), as well BAFF-Receptor, by immunohistochemistry of bioptic specimens of a case-series of patients with proved diagnosis. Methods Nine patients (age range 34-78 yrs) with mean IgG4 serum concentration 548 mg / dl (range 124-1520), 6 with sclerosing pancreatitis, 5 with lymphadenopathy, 4 with sialadenitis, 3 with inflammatory orbital pseudotumor, 2 with dacryoadenitis and 1 with prostate hypertrophy had been enrolled. Bioptic tissue samples have been evaluated by immunohistochemistry with anti-BAFF, anti-BAFF-R, anti-APRIL antibodies and semi-quantitative analysis was performed and Immuno Reactivity Score was used (IRS=% of positive cells x staining intensity). Results APRIL and BAFF were expressed at same level (IRS mean 60.6±40 and 67.5±55, respectively) in tissues biopsies. APRIL and BAFF were localized outside the germinal center, with a cytoplasmic staining. BAFF R (IRS mean 170.6±109) was positive in the lymphocytes agglomerates and inside the germinal centers. Moreover, IgG4 correlates with BAFF R IRS ( r=0.56), and do not correlate with APRIL and BAFF immune staining. Conclusions Our data reinforce the hypothesis of the major role played by B lymphocyte activation in this disease and suggest a possible therapeutical approach by monoclonal antibodies specific for B-lymphocytes activating factors.
I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
