Changed phagocytic activity and pattern of Fcγ and complement receptors on blood monocytes in sarcoidosis

Dubaniewicz, Anna; Typiak, Marlena; Wybieralska, Monika; Szadurska, Marta; Nowakowski, Szymon; Staniewicz-Panasik, Agnieszka; Rogoza, Katarzyna; Sternau, Adam; Deeg, P; Trzonkowski, Piotr

doi:10.1016/j.humimm.2012.05.005

Cited by 44 publications

(38 citation statements)

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“…This is in agreement with previously shown elevated presence of both FcγR class II and III receptors on monocytes in peripheral blood of our patients with sarcoidosis [10]. Moreover, in our previous study we have reported an increase in frequency of functional 57Q allele and 57XQ genotype of FCGR2C gene in Stage III and IV of SA [12].…”

Section: Discussionsupporting

confidence: 93%

“…Activation of these cells results in phagocytosis of ICs and/or bacteria, (auto)antigen presentation, oxidative burst, antibody-dependent cell-mediated cytotoxicity and/or antibody production [19,34]. Subsequently it results in migration of monocytes, macrophages, neutrophils and lymphocytes to the site of inflammation with their proliferation, and may result in formation of a sarcoid granuloma [10]. …”

Section: Discussionmentioning

confidence: 99%

“…However, the increased level of ICs may be as well a result of altered elimination of antigens and ICs due to dysfunction of receptors for Fc fragment of immunoglobulin G (FcγR) from class II and III, important in phagocytosis and clearance of immune complexes [8,9]. Hence, we have analyzed expression of FcγRs on monocytes and phagocytic activity of these cells in our SA patients, revealing an increased number of FcγRII+ and FcγRIII+ monocytes with their higher phagocytic activity, which however did not eliminate circulating ICs [10]. It could point to lowered affinity of FcγRs to ICs due to polymorphism of FCGR genes, encoding Fcγ receptors from classes II and III ( FCGR2A , FCGR2B , FCGR2C , FCGR3A , FCGR3B ), and/or aberration in their copy number (CN), which has been revealed in many other autoimmune disorders, but not yet in SA.…”

Section: Introductionmentioning

confidence: 99%

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Copy number variation of FCGR genes in etiopathogenesis of sarcoidosis

et al. 2017

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We have previously revealed that, in contrast to polymorphism of FCGR2B and FCGR3B, polymorphism of FCGR2A, FCGR2C and FCGR3A genes, encoding receptors for Fc fragment of immunoglobulin G (Fcγ receptors), play a role in increased level of circulating immune complexes with occurrence of Mycobacterium tuberculosis heat shock proteins in patients with sarcoidosis. However, this immunocomplexemia might also be caused by decreased clearance by immune cells due to a changed copy number of FCGR genes. Thus, the next step of our study was to evaluate copy number variation of FCGR2A, FCGR2B, FCGR2C, FCGR3A and FCGR3B in this disease. The analysis was carried out by real-time quantitative PCR on 104 patients and 110 healthy volunteers. Despite previously detected variation in allele/genotype frequencies of FCGR in sarcoidosis and its particular stages, there was no copy number variation of the tested genes between sarcoidosis or its stages and healthy control, as well as between stages themselves. A relevant increase in copy number of FCGR2C and FCGR3B in Stage IV of sarcoidosis vs. other stages and controls was detected, but this observation was based on a limited number of Stage IV patients. Hence, polymorphism of FCGR genes seems to be more important than their copy number variation in etiopathogenesis of sarcoidosis in patients from the Polish population.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Copy number variation of FCGR genes in etiopathogenesis of sarcoidosis

et al. 2017

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“…30 Thus, upregulation of SLAMF8 fits well with the current understanding of the pathogenesis of sarcoidosis. Several other transcripts that we found to be upregulated in the orbit in tissue from patients with sarcoidosis have been implicated in studies on sarcoidosis in other tissues, including Fcγ receptor 1 (CD64 [OMIM 147840]), 37 ICAM-1 (OMIM 146760), 38 and IL-1β (OMIM 147720). 39,40 …”

Section: Discussionmentioning

confidence: 93%

Parallel Gene Expression Changes in Sarcoidosis Involving the Lacrimal Gland, Orbital Tissue, or Blood

et al. 2015

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IMPORTANCE Sarcoidosis is a major cause of ocular or periocular inflammation. The pathogenesis of sarcoidosis is incompletely understood and diagnosis often requires a biopsy.OBJECTIVE To determine how gene expression in either orbital adipose tissue or the lacrimal gland affected by sarcoidosis compares with gene expression in other causes of orbital disease and how gene expression in tissue affected by sarcoidosis compares with gene expression in peripheral blood samples obtained from patients with sarcoidosis. DESIGN, SETTING, AND PARTICIPANTSIn a multicenter, international, observational study, gene expression profiling of formalin-fixed biopsy specimens, using GeneChipp U133 Plus 2 microarrays (Affymetrix), was conducted between October 2012 and January 2014 on tissues biopsied from January 2000 through June 2013. Participants included 12 patients with orbital sarcoidosis (7 in adipose tissue; 5 affecting the lacrimal gland) as well as comparable tissue from 6 healthy individuals serving as controls or patients with thyroid eye disease, nonspecific orbital inflammation, or granulomatosis with polyangiitis. In addition, results were compared with gene expression in peripheral blood samples obtained from 12 historical individuals with sarcoidosis. MAIN OUTCOMES AND MEASURESSignificantly differentially expressed transcripts defined as a minimum of a 1.5-fold increase or a comparable decrease and a false discovery rate of P < .05.RESULTS Signals from 2449 probe sets (transcripts from approximately 1522 genes) were significantly increased in the orbital adipose tissue from patients with sarcoidosis. Signals from 4050 probe sets (approximately 2619 genes) were significantly decreased. Signals from 3069 probe sets (approximately 2001 genes) were significantly higher and 3320 (approximately 2283 genes) were significantly lower in the lacrimal gland for patients with sarcoidosis. Ninety-two probe sets (approximately 69 genes) had significantly elevated signals and 67 probe sets (approximately 56 genes) had significantly lower signals in both orbital tissues and in peripheral blood from patients with sarcoidosis. The transcription factors, interferon-response factor 1, interferon-response factor 2, and nuclear factor κB, were strongly implicated in the expression of messenger RNA upregulated in common in the 3 tissues.CONCLUSIONS AND RELEVANCE Gene expression in sarcoidosis involving the orbit or lacrimal gland can be distinguished from gene expression patterns in control tissue and overlaps with many transcripts upregulated or downregulated in the peripheral blood of patients with sarcoidosis. These observations suggest that common pathogenic mechanisms contribute to sarcoidosis in different sites. The observations support the hypothesis that a pattern of gene expression profiles could provide diagnostic information in patients with sarcoidosis.

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“…Mtb-hsp16, with following persistent antigenemia, immunocomplexemia and increased local proliferation of B-and T-cells with granuloma formation (Fig. 1) [1,3,9,[39][40][41][42][43][44]. The ability of CIs to induce a severe local inflammatory response by synthesis and release of prostaglandins, and hydrolases from phagocytes, may also be an important pathogenic mechanism in SA [43].…”

Section: Discussionmentioning

confidence: 99%