<scp>HLA</scp>‐C: An Accomplice in Rheumatic Diseases

Siegel, Ruby; Bridges, S. Louis; Ahmed, Salahuddin

doi:10.1002/acr2.11065

Cited by 23 publications

(22 citation statements)

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“…Genetic variations in HLA may be the result of evolutionary adaptation in response to environmental stress, such as climate and the prevalence of infectious diseases [63]. HLA-C plays an essential role in the protection against cancers and viruses, and has also been implicated in rheumatic diseases, including psoriasis and psoriatic arthritis [64]. The HLA serotype may also play a role in the global coronavirus pandemic.…”

Section: Hla-cw1 and Infectious Agentsmentioning

confidence: 99%

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HLA-Cw1 and Psoriasis

Huang

Tsai

2021

Am J Clin Dermatol

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Psoriasis is a chronic inflammatory skin condition with regional and ethnic differences in its prevalence and clinical manifestations. Human leukocyte antigen (HLA)-Cw6 is the disease allele conferring the greatest risk to psoriasis, but its prevalence is lower in Asian individuals. Recent studies have found associations between HLA-Cw1 and some Asian populations with psoriasis, especially Southern Chinese. HLA-Cw6 was associated with type I early-onset psoriasis, guttate psoriasis, Koebner phenomenon, and better response to methotrexate, interleukin (IL)-12/23, IL-17, and IL-23 targeting drugs. In contrast, HLA-Cw1 positivity has been associated with erythrodermic psoriasis, pustular psoriasis, and the axial type of psoriatic arthritis. Furthermore, HLA-Cw1 was more frequently associated with high-need patients who did not respond to conventional therapies. No known trigger factor nor autoantigen has been identified for HLA-Cw1 positivity. However, HLA-Cw1 has been linked to some viral agents. For example, cytotoxic T lymphocytes recognize multiple cytomegalovirus pp65-derived epitopes presented by HLA alleles, including HLA-C*01:02. In addition, cytomegalovirus can lead to severe exacerbation of psoriatic skin disease. The proposed interaction between viral infection, HLA-Cw1, and psoriasis is through the killer cell immunoglobulin-like receptors of natural killer cells. Given the diverse nature of psoriasis pathogenesis and the difference in HLA-Cw prevalence in different racial groups, more studies are needed to confirm the role of HLA-Cw1 in psoriasis. Key PointsHuman leukocyte antigen (HLA)-Cw1 is a less recognized but important HLA-Cw allele associated with psoriasis in some Asian ethnicities.Patients carrying HLA-Cw1 tend to show higher disease activity, have an increased risk of developing erythrodermic psoriasis, and are more refractory to treatments.

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Section: Hla-cw1 and Infectious Agentsmentioning

confidence: 99%

“…The proposed function of HLA-C in autoimmune and inflammatory diseases is to present antigens to T cells and to drive the innate immunity through binding activating or inhibitory receptors on NK cells [64]. HLA-Cw1 was increased in patients with various clinical forms of tuberculosis, [66].…”

Section: Hla-cw1 and Infectious Agentsmentioning

confidence: 99%

HLA-Cw1 and Psoriasis

Huang

Tsai

2021

Am J Clin Dermatol

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“…We found some candidate genes that were significantly over-expressed postpartum when RA flared (vs. healthy or RA NoFlare women). Several of those have been implicated in pro-inflammatory processes; for example, HLA-C has been associated with RA [ 31 ]; RNF182 was previously reported to be over-expressed in RA [ 32 ], and TUBB2A was found to be over-expressed in psoriatic arthritis [ 33 ]. Given that the postpartum expression of these genes were dysregulated only during the postpartum flare, and that postpartum expression levels were comparable between healthy and RA NoFlare women, we speculate that these genes may play a role in the postpartum flare of RA.…”

Section: Discussionmentioning

confidence: 99%

Is gene expression among women with rheumatoid arthritis dysregulated during a postpartum flare?

et al. 2021

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Background To evaluate our hypotheses that, when rheumatoid arthritis (RA) flares postpartum, gene expression patterns are altered compared to (a) healthy women, (b) RA women whose disease activity is low or in remission postpartum, and (c) pre-pregnancy expression profiles. Methods Twelve women with RA and five healthy women were included in this pilot study. RA disease activity and postpartum flare were assessed using the Clinical Disease Activity Index (CDAI). Total RNA from frozen whole blood was used for RNA sequencing. Differential gene expression within the same women (within-group) over time, i.e., postpartum vs. third trimester (T3) or pre-pregnancy (T0), were examined, using a significance threshold of q < 0.05 and fold-change ≥ 2. Results Nine of the women with RA experienced a flare postpartum (RAFlare), while three had low disease activity or were in remission (RANoFlare) during that time frame. Numerous immune-related genes were differentially expressed postpartum (vs. T3) during a flare. Fold-changes in expression from T3 to postpartum were mostly comparable between the RAFlare and healthy groups. At 3 months postpartum, compared to healthy women, several genes were significantly differentially expressed only among the RAFlare women, and not among the RANoFlare women. Some of these genes were among those whose “normal” expression was significantly modulated postpartum, and the postpartum expression patterns were significantly altered during the RA flare. There were also some genes that were significantly differentially expressed in RAFlare compared to both healthy and RANoFlare women, even though their expression was not significantly modulated postpartum. Furthermore, while postpartum expression profiles were similar to those at pre-pregnancy among healthy women, significant differences were found between those time points among the RAFlare women. Conclusions The large majority of gene expression changes between T3 and 3 months postpartum among RA women who flared postpartum reflected normal postpartum changes also seen among healthy women. Nonetheless, during a postpartum flare, a set of immune-related genes showed dysregulated expression compared to healthy women and women with RA whose disease activity was low or in remission during the same time frame, while other genes demonstrated significant differences in expression compared to RA pre-pregnancy levels.

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“…The function of HLA‐C is to present antigens to T cells, and to bind to the activation and inhibitory receptors on natural killer cells. It was proven that HLA‐C plays a vital role in prevention for some cancer and viruses, but it is also associated with allograft rejection, preeclampsia and autoimmune diseases 2,3 . Currently, more than 6223 HLA‐C alleles have been identified according to the latest version of IPD‐IMGT/HLA Database (Release 3.42.0, October, 2020) 4 .…”

Section: Figurementioning

confidence: 99%

“…It was proven that HLA-C plays a vital role in prevention for some cancer and viruses, but it is also associated with allograft rejection, preeclampsia and autoimmune diseases. 2,3 Currently, more than 6223 HLA-C alleles have been identified according to the latest version of IPD-IMGT/HLA Database (Release 3.42.0, October, 2020). 4 Here, we describe a new HLA-C allele, now officially named HLA-C*03:04:79, identified using next-generation sequencing in a Chinese bone marrow donor.…”

Section: Introductionmentioning

confidence: 99%

Identification of the novel HLA‐C03:04:79* allele in a Chinese bone marrow donor

Zhang

et al. 2021

HLA

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HLA‐C: An Accomplice in Rheumatic Diseases

Cited by 23 publications

References 84 publications

HLA-Cw1 and Psoriasis

HLA-Cw1 and Psoriasis

Is gene expression among women with rheumatoid arthritis dysregulated during a postpartum flare?

Identification of the novel HLA‐C03:04:79* allele in a Chinese bone marrow donor

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HLA‐C: An Accomplice in Rheumatic Diseases

Cited by 23 publications

References 84 publications

HLA-Cw1 and Psoriasis

HLA-Cw1 and Psoriasis

Is gene expression among women with rheumatoid arthritis dysregulated during a postpartum flare?

Identification of the novel HLA‐C*03:04:79 allele in a Chinese bone marrow donor

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Identification of the novel HLA‐C03:04:79* allele in a Chinese bone marrow donor