title: [Immune mechanism and clinical significance of infection immunity activation for medullary hematopoietic injury of immune-related hematocytopenia syndrome].
abstract: OBJECTIVE
  To observe the pathologic effects of marrow hematopoietic cell with immunologic injury induced by infection immunity activation in patients with immune related hematocytopenia syndrome (IRHS) and elucidate its immunologic mechanism and clinical significance.
  
  
  METHODS
  A total of 276 IRHS patients with acute and chronic infections were recruited from 2008 to 2013. ELISA was used to detect the levels of interleukin-6 (IL-6), IL-12, IL-17 and interferon gamma (IFN-γ) in peripheral blood sera of IRHS patients before and after therapy. Flow cytometry was performed to detect the proportion of lymphocyte subgroups in peripheral blood. Immunochemical staining was used to analyze the expressive states of peroxydase (POX), HLA-DR in bone marrow and non-specific esterase. The expressive states of CD4, CD8, CD56, IFN-γ, porforin, granzyme, FcγRII, anti-human IgG, mannose receptor (MR), IL-12 and IL-17A in bone marrow cells and hematopoietic microenvironment were analyzed with immunofluorescence (IF). According to the above immunological indices, antibiotics were prescribed along with medaron and ciclosporin A (CsA).
  
  
  RESULTS
  Among 276 patients, the levels of IL-6, IL-12, IL-17 and IFN-γ were higher than those in control group (all P < 0.05) . After treatment, the cytokine levels above decreased to normal gradually. The levels of CD3(+) CD4(+) T and NK cells increased respectively in those with concurrent viral or mycoplasma infection(54.23% ± 3.07% and 50.11% ± 3.09% vs 35.25% ± 5.16%, 22.71% ± 2.26% and 19.49% ± 2.07% vs 14.91% ± 4.87%) . The proportions of CD3(+) CD4(+) T and CD19(+) B cells increased in sera of patients with bacterial infection (40.22% ± 4.31% vs 35.25% ± 5.16%, 29.01% ± 4.32% vs 11.56% ± 2.54%) . But the proportion of CD3(+) CD8(+) T cells increased in patients with viral infection of type B hepatitis(32.51% ± 3.44% vs 25.08% ± 4.43%) (all P < 0.05). In patient marrow samples, dendritic cell, T lymphocyte, eosinophilic granulocyte and macrophage were activated to express many above mentioned immunological molecules. Both the destructive pattern of hemocyte and the degree of pathological lesion induced by these immunocytes were related with the cause of infection immunity activation and morbid state of patients. After individualized treatment, 264 patients showed elevated hemogram at 4-8 weeks while the relapse of 12 patients persisted until an initiation of cytotoxic drug and a gradual restoration of hemogram.
  
  
  CONCLUSIONS
  Infection is one of the most important factors of IRHS. Excessive activation of infection immunity may induce the disorder of immune system. Then immunocytes destroy or damage those hemocytes with pathological changes through different immunological pathways. The pathogenetic condition and outcome is related with infected pathogen and intrasubject immune state. Control of pathogenic microorganism infection and glucocorticoid treatment may suppress the excessive activation of immunocytes so as to become important preventive and curing measures of IRHS.
authors.affiliation: Department of Tumor Research & Treatment Centricity, People's Liberation Army No. 148 Hospital, Zibo 255300, China. Email: sunlifei_2007@163.com.
authors.forename: Lifei
authors.initials: L
authors.lastname: Sun
authors.affiliation: Department of Tumor Research & Treatment Centricity, People's Liberation Army No. 148 Hospital, Zibo 255300, China.
authors.forename: Qiangqiang
authors.initials: Q
authors.lastname: Wu
authors.affiliation: Department of Tumor Research & Treatment Centricity, People's Liberation Army No. 148 Hospital, Zibo 255300, China.
authors.forename: Hongfeng
authors.initials: H
authors.lastname: Hao
authors.affiliation: Department of Tumor Research & Treatment Centricity, People's Liberation Army No. 148 Hospital, Zibo 255300, China.
authors.forename: Yanhui
authors.initials: Y
authors.lastname: Du
authors.affiliation: Department of Tumor Research & Treatment Centricity, People's Liberation Army No. 148 Hospital, Zibo 255300, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Ming
authors.affiliation: Department of Tumor Research & Treatment Centricity, People's Liberation Army No. 148 Hospital, Zibo 255300, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Xu
authors.affiliation: Department of Tumor Research & Treatment Centricity, People's Liberation Army No. 148 Hospital, Zibo 255300, China.
authors.forename: Guichen
authors.initials: G
authors.lastname: Wang
authors.affiliation: Department of Tumor Research & Treatment Centricity, People's Liberation Army No. 148 Hospital, Zibo 255300, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Tumor Research & Treatment Centricity, People's Liberation Army No. 148 Hospital, Zibo 255300, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001854:Bone Marrow Cells / Q000166:cytology / Q000473:pathology*; D016207:Cytokines / Q000097:blood; D005260:Female; D006410:Hematopoiesis; D006801:Humans; D007239:Infections / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D010198:Pancytopenia / Q000276:immunology*; D013577:Syndrome; D055815:Young Adult
chemical_list: D016207:Cytokines