OBJECTIVE: To study the prevalence, clinical associations, and functional implications of the His159Tyr mutation of the BAFF receptor (BAFF-R) in patients with Sjögren's syndrome (SS). METHODS: The BAFF-R His159Tyr mutation was evaluated using polymerase chain reaction (PCR)-based assays in 247 patients with SS (of whom 70 had SS complicated by lymphoma [SS-lymphoma]), 145 with systemic lupus erythematosus (SLE), and 101 with rheumatoid arthritis (RA), as well as 180 healthy controls. Real-time PCR and Western blotting were performed for the quantification of both NF-κB1 and NF-κB2 messenger RNA (mRNA) transcript and protein levels in isolated B cells from patients with SS-lymphoma carrying the mutation (SS-lymphoma-BAFF-RHis159Tyr -derived B cells) compared to B cells from patients with SS-lymphoma who were not carriers of the mutation and healthy controls. RESULTS: Both the SS-lymphoma and SS-nonlymphoma patient subgroups exhibited significantly higher frequencies of the His159Tyr BAFF-R mutation compared to healthy controls (8.6% of SS-lymphoma patients and 6.2% of SS-nonlymphoma patients versus 1.7% of healthy controls; P = 0.02 and P = 0.04, respectively). The corresponding frequencies of the His159Tyr BAFF-R mutation in SLE and RA patients were 3.5% and 3%, respectively. Of interest, 71.4% of the SS patients with mucosa-associated lymphoid tissue (MALT) lymphoma who were between the ages of 31 and 40 years at disease onset were mutation carriers. The generalized odds ratio for the development of SS-related MALT lymphoma in the younger age at onset (age <40 years) group in the presence of the BAFF-R mutation was 6.1 (95% confidence interval 2.0-18.7) (P < 0.01). Expression of NF-κB at both the mRNA and protein level was up-regulated in SS-lymphoma-BAFF-RHis159Tyr -derived B cells. CONCLUSION: This study identifies an increased prevalence of the BAFF-R His159Tyr mutation in patients with SS, particularly in those with SS complicated by MALT lymphoma whose disease onset occurred at a younger age. BAFF-RHis159Tyr -mediated activation of the alternate NF-κB pathway might contribute to the pathogenesis of SS-related lymphoproliferative disease.
OBJECTIVE: To study the prevalence, clinical associations, and functional implications of the His159Tyr mutation of the BAFF receptor (BAFF-R) in patients with Sjögren's syndrome (SS). METHODS: The BAFF-RHis159Tyr mutation was evaluated using polymerase chain reaction (PCR)-based assays in 247 patients with SS (of whom 70 had SS complicated by lymphoma [SS-lymphoma]), 145 with systemic lupus erythematosus (SLE), and 101 with rheumatoid arthritis (RA), as well as 180 healthy controls. Real-time PCR and Western blotting were performed for the quantification of both NF-κB1 and NF-κB2 messenger RNA (mRNA) transcript and protein levels in isolated B cells from patients with SS-lymphoma carrying the mutation (SS-lymphoma-BAFF-RHis159Tyr -derived B cells) compared to B cells from patients with SS-lymphoma who were not carriers of the mutation and healthy controls. RESULTS: Both the SS-lymphoma and SS-nonlymphomapatient subgroups exhibited significantly higher frequencies of the His159TyrBAFF-R mutation compared to healthy controls (8.6% of SS-lymphomapatients and 6.2% of SS-nonlymphoma patients versus 1.7% of healthy controls; P = 0.02 and P = 0.04, respectively). The corresponding frequencies of the His159TyrBAFF-R mutation in SLE and RApatients were 3.5% and 3%, respectively. Of interest, 71.4% of the SS patients with mucosa-associated lymphoid tissue (MALT) lymphoma who were between the ages of 31 and 40 years at disease onset were mutation carriers. The generalized odds ratio for the development of SS-related MALT lymphoma in the younger age at onset (age <40 years) group in the presence of the BAFF-R mutation was 6.1 (95% confidence interval 2.0-18.7) (P < 0.01). Expression of NF-κB at both the mRNA and protein level was up-regulated in SS-lymphoma-BAFF-RHis159Tyr -derived B cells. CONCLUSION: This study identifies an increased prevalence of the BAFF-RHis159Tyr mutation in patients with SS, particularly in those with SS complicated by MALT lymphoma whose disease onset occurred at a younger age. BAFF-RHis159Tyr -mediated activation of the alternate NF-κB pathway might contribute to the pathogenesis of SS-related lymphoproliferative disease.
Authors: Adrianos Nezos; Fotini Gravani; Anna Tassidou; Efstathia K Kapsogeorgou; Michael Voulgarelis; Michael Koutsilieris; Mary K Crow; Clio P Mavragani Journal: J Autoimmun Date: 2015-07-14 Impact factor: 7.094
Authors: Konstantina D Kourou; Vasileios C Pezoulas; Eleni I Georga; Themis Exarchos; Costas Papaloukas; Michalis Voulgarelis; Andreas Goules; Andrianos Nezos; Athanasios G Tzioufas; Earalampos M Moutsopoulos; Clio Mavragani; Dimitrios I Fotiadis Journal: IEEE Open J Eng Med Biol Date: 2020-02-14
Authors: Cesare Mazzaro; Luigino Dal Maso; Laura Gragnani; Marcella Visentini; Francesco Saccardo; Davide Filippini; Pietro Andreone; Anna Linda Zignego; Valter Gattei; Giuseppe Monti; Massimo Galli; Luca Quartuccio Journal: Viruses Date: 2021-05-30 Impact factor: 5.048