The importance of differences; On environment and its interactions with genes and immunity in the causation of rheumatoid arthritis

Klareskog, Lars; Rönnelid, Johan; Saevarsdóttir, Saedís; Padyukov, Leonid; Alfredsson, Lars

doi:10.1111/joim.13058

Cited by 53 publications

(38 citation statements)

References 192 publications

(294 reference statements)

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“…Our results suggest that CHDP may be disparately regulated in airway inflammation compared to inflammatory arthritis. Although the immunopathology of airway inflammation (such as in asthma) and arthritis have been shown to be interconnected (13,14), our results indicate that cathelicidin and calprotectin expression and related functions may not be one of the overlapping molecular mechanisms of immune dysregulation in these two disease processes. The mechanisms related to the differential regulation of CHDP in airway inflammation compared to arthritis warrants further investigation.…”

Section: Discussionmentioning

confidence: 67%

“…Recent evidence suggests the involvement of airway inflammation to the onset and the immunopathology of RA (13,14). Environmental factors such as smoking and air pollution that lead to the exacerbation of airway inflammation are also critical risk factors for the development of RA (13). Thus, although airway inflammation and inflammatory arthritis have distinct phenotype, these exhibit overlapping molecular mechanisms of immune dysregulation.…”

Section: Introductionmentioning

confidence: 99%

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Cathelicidin and Calprotectin Are Disparately Altered in Murine Models of Inflammatory Arthritis and Airway Inflammation

et al. 2020

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Cationic host defense peptides (CHDP) are immunomodulatory molecules that control infections and contribute to immune homeostasis. CHDP such as cathelicidin and calprotectin expression is altered in the arthritic synovium, and in the lungs of asthma and COPD patients. Recent studies suggest a link between airway inflammation and the immunopathology of arthritis. Therefore, in this study we compared the abundance of mouse cathelicidin (CRAMP), defensins, and calprotectin subunits (S100A8 and S100A9) in murine models of collagen-induced arthritis (CIA) and allergen house dust mite (HDM)-challenged airway inflammation. CRAMP, S100A8, and S100A9 abundance were significantly elevated in the joint tissues of CIA mice, whereas these were decreased in the lung tissues of HDM-challenged mice, compared to naïve. We further compared the effects of administration of two different synthetic immunomodulatory peptides, IG-19 and IDR-1002, on cathelicidin and calprotectin abundance in the two models. Administration of IG-19, which controls disease progression and inflammation in CIA mice, significantly decreased CRAMP, S100A8, and S100A9 levels to baseline in the joints of the CIA mice, which correlated with the decrease in cellular influx in the joints. However, administration of IDR-1002, which suppresses HDM-induced airway inflammation, did not prevent the decrease in the levels of cathelicidin and calprotectin in the lungs of HDM-challenged mice. Cathelicidin and calprotectin levels did not correlate with leukocyte accumulation in the lungs of the HDM-challenged mice. Results of this study suggest that endogenous cathelicidin and calprotectin abundance are disparately altered, and may be differentially regulated, within local tissues in airway inflammation compared to arthritis.

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Section: Discussionmentioning

confidence: 67%

Section: Introductionmentioning

confidence: 99%

Cathelicidin and Calprotectin Are Disparately Altered in Murine Models of Inflammatory Arthritis and Airway Inflammation

et al. 2020

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“…Protein tyrosine phosphatase, non-receptor type 22 gene (PTPN22) represents a specific lymphophosphatase that plays an important role in T cell signaling due to its inhibiting effect [15,16]. It was implicated in the etiology of various autoimmune diseases, including RA [15,17,18].…”

Section: Introductionmentioning

confidence: 99%

rs2476601 in PTPN22 gene in rheumatoid arthritis and periodontitis—a possible interface?

et al. 2020

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Background Rheumatoid arthritis (RA) and periodontitis (PD) are proven to share common risk markers, including genetic factors. In the present study we focused on genetic variants in PTPN22 (rs2476601), PADI4 (rs2240340), CTLA4 genes (rs3087243) and its impact on RA and PD. Materials and methods In the study 111 RA patients and 256 systemically healthy controls were involved. A subdivision of patients and controls was carried out according the severity of periodontitis (no/level 1 PD vs. level 2 PD). Results I. Evaluating the genetic impact on the occurrence of RA the T allele of rs2476601 (PTPN22) (bivariate: p < 0.001; multivariate: p = 0.018) and T allele of rs2240340 (PADI4) (bivariate: p = 0.006; multivariate: p = 0.070) were associated with an increased vulnerability to RA. II. Investigating the genetic influence on level 2 PD the T allele of rs2476601 (PTPN22) was shown to be associated with a higher susceptibility to PD within the RA group (bivariate: p = 0.043; multivariate: p = 0.024). III. The T allele of rs2476601 (PTPN22) was proven to be a significant marker of RA and level 2 PD comorbidity (bivariate: p < 0.001; multivariate: p = 0.028). Conclusions These results support the thesis that genetic variations may represent a possible link between PD and RA. The study increases knowledge about disease-specific and cross-disease genetic pattern.

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“…There is a clear genetic basis to RA but its underlying mechanisms remain unknown (9). Recently, an increasing number of studies have attempted to reveal the important role of epigenetics in the pathogenesis of RA (10,11).…”

Section: Introductionmentioning

confidence: 99%

Prediction of Self-Perception of Patient in Rheumatoid Arthritis With the Key RNAs Expression Profiles

et al. 2020

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Self-perception in patients is their self-response to sensory stimuli. It is an important aspect of the existence and quality of life among patients. However, the inherent relationship between self-perception and the cellular activity at the molecular level is elusive. In this study, we aimed to explore the association of self-perception with RNA expression profile in patients with rheumatoid arthritis (RA) through computational analysis. We recruited 30 patients clinically diagnosed with RA and to age-and sex-matched controls without previous clinical history. In total, 5 self-perception measures and 30 RNA expression measures were derived from RA patients and control groups. A correlation analysis based on Spearman correlation and Logistic-regression methods was adopted to assess the correlation between self-perception and RNA expression. Quantitative analysis revealed that RA patients with poor self-perception were closely associated with RNAs expression, In addition, 3 key molecules including AC019117.2, LINC00638, and hsa_circ_0003972 could be used to predict self-perception changes in RA patients. Herein, our results will provide new insights in RA diagnosis however, the underlying mechanisms need to be further explored.

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The importance of differences; On environment and its interactions with genes and immunity in the causation of rheumatoid arthritis

Abstract: Klareskog L, R€ onnelid

Cited by 53 publications

References 192 publications

Cathelicidin and Calprotectin Are Disparately Altered in Murine Models of Inflammatory Arthritis and Airway Inflammation

Cathelicidin and Calprotectin Are Disparately Altered in Murine Models of Inflammatory Arthritis and Airway Inflammation

rs2476601 in PTPN22 gene in rheumatoid arthritis and periodontitis—a possible interface?

Prediction of Self-Perception of Patient in Rheumatoid Arthritis With the Key RNAs Expression Profiles

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