PMID- 28183334 OWN - NLM STAT- MEDLINE DCOM- 20171109 LR - 20181113 IS - 1478-6362 (Electronic) IS - 1478-6354 (Print) IS - 1478-6354 (Linking) VI - 19 IP - 1 DP - 2017 Feb 10 TI - Circulating plasmablasts/plasma cells: a potential biomarker for IgG4-related disease. PG - 25 LID - 10.1186/s13075-017-1231-2 [doi] LID - 25 AB - BACKGROUND: Immunoglobulin G4 (IgG4)-related disease (IgG4-RD) is a multisystem fibroinflammatory disease. We previously reported that a circulating cell population expressing CD19(+)CD24(-)CD38(hi) was increased in patients with IgG4-RD. In this study, we aimed to document that this cell population represented circulating plasmablasts/plasma cells, to identify the detailed phenotype and gene expression profile of these IgG4-secreting plasmablasts/plasma cells, and to determine whether this B-cell lineage subset could be a biomarker in IgG4-related disease (IgG4-RD). METHODS: A total of 42 untreated patients with IgG4-RD were evaluated. Peripheral B-cell subsets, including CD19(+)CD24(-)CD38(hi) plasmablasts/plasma cells, CD19(+)CD24(+)CD38(-) memory B cells, CD19(+)CD24(int)CD38(int) naive B cells, and CD19(+)CD24(hi)CD38(hi) regulatory B cells, were assessed and sorted by flow cytometry. Microarray analysis was used to measure gene expression of circulating B-cell lineage subsets. Further characterization of CD19(+)CD24(-)CD38(hi) plasmablasts/plasma cells was carried out by evaluating additional surface markers, including CD27, CD95, and human leukocyte antigen (HLA)-DR, by flow cytometric assay. In addition, various B-cell lineage subsets were cultured in vitro and IgG4 concentrations were measured by cytometric bead array. RESULTS: In untreated patients with IgG4-RD, the peripheral CD19(+)CD24(-)CD38(hi) plasmablast/plasma cell subset was increased and positively correlated with serum IgG4 levels, the number of involved organs, and the IgG4-related Disease Responder Index. It decreased after treatment with glucocorticoids. Characterization of the plasmablast/plasma cell population by gene expression profiling documented a typical plasmablast/plasma cell signature with higher expression of X-box binding protein 1 and IFN regulatory factor 4, but lower expression of paired box gene 5 and B-cell lymphoma 6 protein. In addition, CD27, CD95, and HLA-DR were highly expressed on CD19(+)CD24(-)CD38(hi) plasmablasts/plasma cells from patients with IgG4-RD. Furthermore, CD19(+)CD24(-)CD38(hi) plasmablasts/plasma cells secreted more IgG4 than other B-cell populations. CONCLUSIONS: Circulating CD19(+)CD24(-)CD38(hi) plasmablasts/plasma cells are elevated in active IgG4-RD and decreased after glucocorticoid treatment. This IgG4-secreting plasmablast/plasma cell population might be a potentially useful biomarker for diagnosis and assessing response to treatment. FAU - Lin, Wei AU - Lin W AD - Department of Rheumatology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, 100730, China. AD - Department of Rheumatology, Hebei General Hospital, Shijiazhuang, China. FAU - Zhang, Panpan AU - Zhang P AD - Department of Rheumatology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, 100730, China. FAU - Chen, Hua AU - Chen H AD - Department of Rheumatology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, 100730, China. FAU - Chen, Yu AU - Chen Y AD - Department of Rheumatology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, 100730, China. FAU - Yang, Hongxian AU - Yang H AD - Department of Rheumatology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, 100730, China. FAU - Zheng, Wenjie AU - Zheng W AD - Department of Rheumatology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, 100730, China. FAU - Zhang, Xuan AU - Zhang X AD - Department of Rheumatology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, 100730, China. FAU - Zhang, Fengxiao AU - Zhang F AD - Department of Rheumatology, Hebei General Hospital, Shijiazhuang, China. FAU - Zhang, Wen AU - Zhang W AD - Department of Rheumatology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, 100730, China. zhangwen91@sina.com. FAU - Lipsky, Peter E AU - Lipsky PE AD - National Institutes of Health, Bethesda, MD, USA. peterlipsky@comcast.net. LA - eng PT - Journal Article DEP - 20170210 PL - England TA - Arthritis Res Ther JT - Arthritis research & therapy JID - 101154438 RN - 0 (Biomarkers) RN - 0 (Immunoglobulin G) SB - IM MH - Adult MH - Biomarkers/blood MH - Female MH - Flow Cytometry MH - Humans MH - Immune System Diseases/*immunology MH - Immunoglobulin G/*immunology MH - Male MH - Middle Aged MH - Oligonucleotide Array Sequence Analysis MH - Plasma Cells/*immunology PMC - PMC5301376 OTO - NOTNLM OT - Autoimmunity OT - Biomarker OT - CD19+CD24-CD38hi plasmablast/plasma cell OT - IgG4-RD EDAT- 2017/02/12 06:00 MHDA- 2017/11/10 06:00 PMCR- 2017/02/10 CRDT- 2017/02/11 06:00 PHST- 2016/08/24 00:00 [received] PHST- 2017/01/12 00:00 [accepted] PHST- 2017/02/11 06:00 [entrez] PHST- 2017/02/12 06:00 [pubmed] PHST- 2017/11/10 06:00 [medline] PHST- 2017/02/10 00:00 [pmc-release] AID - 10.1186/s13075-017-1231-2 [pii] AID - 1231 [pii] AID - 10.1186/s13075-017-1231-2 [doi] PST - epublish SO - Arthritis Res Ther. 2017 Feb 10;19(1):25. doi: 10.1186/s13075-017-1231-2.