CD163 expression is increased in the involved skin and sera of patients with systemic lupus erythematosus

Nakayama, Wakana; Jinnin, Masatoshi; Makino, Katsunari; Kajihara, Ikko; Makino, Takamitsu; Fukushima, Satoshi; Sakai, Keisuke; Inoue, Yuji; Ihn, Hironobu

doi:10.1684/ejd.2012.1756

Cited by 33 publications

(24 citation statements)

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“…We also have shown a direct correlation of sMer with sCD163 levels and a significant correlation between SLEDAI and sCD163 levels. Our data strongly suggest a strict relation between SLE activity and M2c homeostasis, in agreement with recent data from Nakayama et al showing sCD163 associations with anti-dsDNA positivity and leukopenia [30]. Similarities between sMer and sCD163, with regard to their expression patterns and their associations in SLE, are consistent with the fact that their respective membrane receptors MerTK and CD163 are both upregulated on the surface of regulatory M2c monocytes/macrophages [9].…”

Section: Discussionsupporting

confidence: 92%

Circulating levels of soluble MER in lupus reflect M2c activation of monocytes/macrophages, autoantibody specificities and disease activity

et al. 2013

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IntroductionSystemic lupus erythematosus (SLE) is characterized by impaired efferocytosis and aberrant activation of innate immunity. We asked if shedding of MER receptor tyrosine kinase (MerTK) and AXL into soluble (s) ectodomains was related to immunological and clinical aspects of SLE.MethodsLevels of sMER and sAXL in the plasma of 107 SLE patients and 45 matched controls were measured by ELISA. In 40 consecutive SLE patients, we examined potential correlations between either sMER or sAXL and plasma levels of sCD163, a marker of M2 activation. All three soluble receptors were measured in supernatants of monocytes/macrophages cultured in various immunological conditions. Membrane expression of MerTK, AXL and CD163 was assessed by flow cytometry.ResultsBoth sMER and sAXL were associated with anti-chromatin and anti-phospholipid autoantibodies, and with hematological and renal involvement. However, sMER and sAXL did not significantly correlate with each other; sAXL correlated with growth arrest-specific 6 (Gas6), whereas sMER correlated with reduced free protein S (PROS) levels. Only sMER showed significant associations with lupus-specific anti-dsDNA, anti-Sm, anti-ribonucleoprotein (anti-RNP) and anti-Ro60 autoantibodies. Strong correlations with disease activity indices (Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), complement reduction, titer of circulating anti-dsDNA) were found for sMER, not for sAXL. Patients with active SLEDAI, nephritis, anti-dsDNA and anti-Ro60 positivity showed higher levels of sMER compared to controls. Levels of sMER, not sAXL, correlated with sCD163 levels, and these correlated with SLEDAI. Production of sMER and sCD163 occurred under “M2c” polarizing conditions, whereas sAXL was released upon type-I IFN exposure.ConclusionsAlterations in homeostasis of anti-inflammatory and efferocytic “M2c” monocytes/macrophages may have a role in immunopathogenesis of SLE.

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Section: Discussionsupporting

confidence: 92%

Circulating levels of soluble MER in lupus reflect M2c activation of monocytes/macrophages, autoantibody specificities and disease activity

et al. 2013

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“…Whether other organ involvement in SLE could influence the level of urine sCD163 has been questioned. Of relevance, serum/plasma level of sCD163 was significantly higher in SLE compared to healthy controls, and it correlated with anti-dsDNA antibodies, anti-chromatin antibodies, leukopenia, and SLEDAI (9,30,31). However, elevated plasma sCD163 levels in LN were not associated with ISN/RPS class (23), suggesting that increased urine sCD163 is unlikely to be the consequence of enhanced leakage of circulating sCD163 or systemic activation of macrophages, although this needs to be examined more systematically.…”

Section: Discussionmentioning

confidence: 93%

Association of Urine sCD163 With Proliferative Lupus Nephritis, Fibrinoid Necrosis, Cellular Crescents and Intrarenal M2 Macrophages

et al. 2020

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CD163 is a marker for alternatively activated macrophages, which have been implicated in the pathogenesis of lupus nephritis (LN). In our preliminary screening of urine proteins in LN, urine soluble CD163 (sCD163) was significantly elevated in patients with active LN. To evaluate the potential of sCD163 as a biomarker in LN, urine sCD163 was assayed in patients with active LN, active non-renal lupus patients (ANR), inactive SLE and healthy controls (HC), using ELISA and normalized to urine creatinine. The correlation of urine sCD163 with clinical parameters and renal pathological attributes was further investigated in LN patients with concurrent renal biopsies. A total of 228 SLE patients and 56 HC were included from three cohorts. Results demonstrated that urine sCD163 was significantly elevated in active LN when compared with HC, inactive SLE, or ANR in African-American, Caucasian and Asian subjects (all P < 0.001). In LN patients with concurrent renal biopsies, urine sCD163 was significantly increased in patients with proliferative LN when compared with non-proliferative LN (P < 0.001). Urine sCD163 strongly correlated with SLEDAI, rSLEDAI, activity index (AI) of renal pathology, fibrinoid necrosis, cellular crescents, and interstitial inflammation on biopsies (all P < 0.01). Macrophages, particularly M2 macrophages, the predominant cells expressing CD163 within LN kidneys, represented a potential source of elevated urine sCD163, based on single-cell RNA sequencing analysis. To conclude, urine sCD163 discriminated patients with active LN from other SLE patients and was significantly elevated in proliferative LN. It strongly correlated with concurrent AI and several specific pathological attributes, demonstrating its potential in predicting renal pathology.

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“…Since then, many studies have found evidence of monocyte/ macrophage activation in SSc. Higher numbers of macrophages have been observed in skin from SSc patients [27,61] while cells positive for CD163, a putative marker for M2 macrophages [62], have been found to be increased in the serum of SSc patients [61,[63][64][65]. M2 macrophages are therefore prominent in SSc, with a very recent study involving more than 200 SSc patients, not only confirming this but also demonstrating that soluble CD163 (sCD163) is significantly elevated in the serum of SSc patients and therefore may be of use as a biomarker [66].…”

Section: Macrophagesmentioning

confidence: 99%

The immunopathogenesis of fibrosis in systemic sclerosis

Brown

O’Reilly

2018

Clinical and Experimental Immunology

141

113

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Summary Systemic sclerosis (SSc) is an idiopathic systemic autoimmune disease. It is characterized by a triad of hallmarks: immune dysfunction, fibrosis and vasculopathy. Immune dysfunction in SSc is characterized by the activation and recruitment of immune cells and the production of autoantibodies and cytokines. How immune abnormalities link the fibrosis and vasculopathy in SSc is poorly understood. A plethora of immune cell types are implicated in the immunopathogenesis of SSc, including T cells, B cells, dendritic cells, mast cells and macrophages. How these different cell types interact to contribute to SSc is complicated, and can involve cell‐to‐cell interactions and communication via cytokines, including transforming growth factor (TGF)‐β, interleukin (IL)‐6 and IL‐4. We will attempt to review significant and recent research demonstrating the importance of immune cell regulation in the immunopathogenesis of SSc with a particular focus on fibrosis.

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CD163 expression is increased in the involved skin and sera of patients with systemic lupus erythematosus

Cited by 33 publications

References 0 publications

Circulating levels of soluble MER in lupus reflect M2c activation of monocytes/macrophages, autoantibody specificities and disease activity

Circulating levels of soluble MER in lupus reflect M2c activation of monocytes/macrophages, autoantibody specificities and disease activity

Association of Urine sCD163 With Proliferative Lupus Nephritis, Fibrinoid Necrosis, Cellular Crescents and Intrarenal M2 Macrophages

The immunopathogenesis of fibrosis in systemic sclerosis

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