Autoantibodies to killer cell immunoglobulin-like receptor 3DL1 in patients with systemic lupus erythematosus

Doi, Ai; Kano, Shogo; Asano, Masanao; Takahashi, Yuko; Mimori, Tsuneyo; Matsubara, Akio; Kaneko, Hiroshi

doi:10.1111/cei.13235

Cited by 4 publications

(2 citation statements)

References 31 publications

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“…NK cells in lupus patients might had turned hyperactive due to lowered expression of KIR3DL1 accompanied by increased expression of KIR2DL4 on its surface, leading to disease exacerbation. Report on the presence of anti-KIR3DL1 antibodies in the serum of SLE patients 43 suggests a link to the decline in KIR3DL1 + CD56 dim cells in lupus patients in our study. While studying the relationship between oxidative stress and KIRs, we noticed KIR3DL1 + CD56 bright cells associated with oxidative stress levels in the plasma of patients.…”

Section: Discussionsupporting

confidence: 70%

Altered oxidative stress markers in relation to T cells, NK cells & killer immunoglobulin receptors that are associated with disease activity in SLE patients

Tandon

Anupam

Kaushal

et al. 2020

Lupus

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Systemic Lupus Erythematosus is an autoimmune disease with symptoms pervasive to all organ systems. It affects more females as compared to males (in the ratio 9:1). Oxidative stress plays a major role in the pathogenesis of SLE and other autoimmune diseases. In order to understand the relationship between cell specific oxidative stress and the severity of SLE, this research study involving the estimation of intracellular ROS accumulation in T and NK cell was conducted on SLE patients of North Indian Population. At the same time, to estimate anti-oxidant defense, Keap1 and Nrf2 levels were estimated in these cell types. The relationship between the expression of Killer immunoglobulin receptors i.e., KIR2DL4 & KIR3DL1 and oxidative stress was also evaluated as these receptors are imperative for the function and self-tolerance of NK cells. Oxidative stress was raised along with Keap1 and Nrf2 in T and NK cell subsets in SLE patients. The expression of KIR2DL4 was raised and that of KIR3DL1 was reduced in the NK cells of patients. The intensity of change in expression and its significance varied among the subsets. Nrf2 expression was raised in these species against oxidative stress as the antioxidant defense mechanism pertaining to Keap1-Nrf2 pathway, but the adequacy of response needs to be understood in further studies. The expression of KIR2DL4 and KIR3DL1 varied among the patient and healthy controls and the expression of the latter was found to have a significant positive relationship with plasma Glutathione(reduced) concentration.

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Section: Discussionsupporting

confidence: 70%

Altered oxidative stress markers in relation to T cells, NK cells & killer immunoglobulin receptors that are associated with disease activity in SLE patients

Tandon

Anupam

Kaushal

et al. 2020

Lupus

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“…These data are line with a previous study, which described antibodies reacting with KIR2DL1 or KIR2DL3-receptors in 7 of 30 (23.3%) SLE patients by probing SLE sera for reactivity to E. coli -derived recombinant KIR2DL1 and KIR2DL3 in Western blot (35). A recent study demonstrated autoantibodies to KIR3DL1 in 22 of 28 SLE sera analyzed with ELISA using recombinant KIR3DL1 (36). In addition to confirming the presence of anti-KIR autoantibodies in SLE patients, our data demonstrate that these autoantibodies react with natively folded membrane-bound KIRs expressed on human cells, and that reactivity to KIR2DL2, KIR3DL2, KIR2DS2, KIR2DS4, and KIR2DL4 is also present in SLE patients.…”

Section: Discussionmentioning

confidence: 99%

Autoantibodies to Killer Cell Immunoglobulin-Like Receptors in Patients With Systemic Lupus Erythematosus Induce Natural Killer Cell Hyporesponsiveness

et al. 2019

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Natural killer (NK) cell cytotoxicity toward self-cells is restrained by the inhibitory HLA class I-binding receptors CD94/NKG2A and the killer cell immunoglobulin-like receptors (KIRs). CD94/NKG2A and KIRs are also essential for NK cell education, which is a dynamic functional maturation process where a constitutive binding of inhibitory receptors to cognate HLA class I molecules is required for NK cells to maintain their full cytotoxic capacity. Previously, we described autoantibodies to CD94/NKG2A in patients with systemic lupus erythematosus (SLE). In this study we analyzed sera from 191 patients with SLE, 119 patients with primary Sjögren's syndrome (pSS), 48 patients with systemic sclerosis (SSc), and 100 healthy donors (HD) for autoantibodies to eight different KIRs. Anti-KIR autoantibodies were identified in sera from 23.0% of patients with SLE, 10.9% of patients with pSS, 12.5% of patients with SSc, and 3.0% of HD. IgG from anti-KIR-positive SLE patients reduced the degranulation and cytotoxicity of NK cells toward K562 tumor cells. The presence of anti-KIR-autoantibodies reacting with >3 KIRs was associated with an increased disease activity (p < 0.0001), elevated serum levels of IFN-α (p < 0.0001), nephritis (p = 0.001), and the presence of anti-Sm (p = 0.007), and anti-RNP (p = 0.003) autoantibodies in serum. Together these findings suggest that anti-KIR autoantibodies may contribute to the reduced function of NK cells in SLE patients, and that a defective NK cell function may be a risk factor for the development of lupus nephritis.

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TMT-based quantitative proteomics analysis and potential serum protein biomarkers for systemic lupus erythematosus

Zhou

Wei

Lan

et al. 2022

Clinica Chimica Acta

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Autoantibodies to killer cell immunoglobulin-like receptor 3DL1 in patients with systemic lupus erythematosus

Cited by 4 publications

References 31 publications

Altered oxidative stress markers in relation to T cells, NK cells & killer immunoglobulin receptors that are associated with disease activity in SLE patients

Altered oxidative stress markers in relation to T cells, NK cells & killer immunoglobulin receptors that are associated with disease activity in SLE patients

Autoantibodies to Killer Cell Immunoglobulin-Like Receptors in Patients With Systemic Lupus Erythematosus Induce Natural Killer Cell Hyporesponsiveness

TMT-based quantitative proteomics analysis and potential serum protein biomarkers for systemic lupus erythematosus

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