The role of killer-cell immunoglobulin-like receptors in systemic autoimmune disease
Introduction. Killer Cell Immunoglobulin-like Receptors (KIRs) are expressed on natural killer (NK) cell and memory T cell subsets and display varying degrees of specificity for HLA class I molecules. KIRs genes are highly polymorphic, exhibiting extensive variation both in the number of genes per h...
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Published in | Genes and immunity Vol. 6; p. S48 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
01.04.2005
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Abstract | Introduction. Killer Cell Immunoglobulin-like Receptors (KIRs) are expressed on natural killer (NK) cell and memory T cell subsets and display varying degrees of specificity for HLA class I molecules. KIRs genes are highly polymorphic, exhibiting extensive variation both in the number of genes per haplotype and allelic variation at each locus. KIRs exert either an activatory or an inhibitory effect upon cellular function following HLA ligand binding (importantly, KIRs and their ligands are not genetically linked). Inhibitory KIRs prevent NK cell mediated attack on normal cells, an effect modulated by the strong affinity of inhibitory KIRs for HLA class I. Recent studies have shown KIR polymorphisms to have a direct effect upon the outcome of haematopoietic stem cell transplantation, viral resistance, and in the development and progression of certain autoimmune disorders. Method. This study investigated polymorphism of KIR genes and their HLA ligand expression in three related systemic autoimmune diseases, each with a common genetic association to HLA -A1, B8, DR3. Seventy Primary Sjogren's syndrome (PSS), 320 Scleroderma (SSc), and 74 Systemic Lupus Erythematosus (SLE) patients were analysed for KIR genes and HLA ligand type using polymerase chain reaction sequence-specific primers (PCR-SSP). These patient groups were compared with a control panel of 223 healthy blood donors. Results. The following differences between patient and control groups were observed. 1. In SSc a significantly low frequency of KIR2DL1 (78% vs. 92%, p=0.05) 2. In PSS a significantly high frequency of KIR2DS2 without KIR2DL2 (15.71% vs 4.9%, p=0.01). 3. No significant differences were found in the SLE group. Conclusion. This study shows that KIRs have a role in certain, but not all, systemic autoimmune diesease. These three diseases have overlapping clinical features as well as other common genetic features (preponderance of females, HLA-A1,B8,DR3). Despite this the KIR associations for these three diseases are clearly different. |
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AbstractList | Introduction. Killer Cell Immunoglobulin-like Receptors (KIRs) are expressed on natural killer (NK) cell and memory T cell subsets and display varying degrees of specificity for HLA class I molecules. KIRs genes are highly polymorphic, exhibiting extensive variation both in the number of genes per haplotype and allelic variation at each locus. KIRs exert either an activatory or an inhibitory effect upon cellular function following HLA ligand binding (importantly, KIRs and their ligands are not genetically linked). Inhibitory KIRs prevent NK cell mediated attack on normal cells, an effect modulated by the strong affinity of inhibitory KIRs for HLA class I. Recent studies have shown KIR polymorphisms to have a direct effect upon the outcome of haematopoietic stem cell transplantation, viral resistance, and in the development and progression of certain autoimmune disorders. Method. This study investigated polymorphism of KIR genes and their HLA ligand expression in three related systemic autoimmune diseases, each with a common genetic association to HLA -A1, B8, DR3. Seventy Primary Sjogren's syndrome (PSS), 320 Scleroderma (SSc), and 74 Systemic Lupus Erythematosus (SLE) patients were analysed for KIR genes and HLA ligand type using polymerase chain reaction sequence-specific primers (PCR-SSP). These patient groups were compared with a control panel of 223 healthy blood donors. Results. The following differences between patient and control groups were observed. 1. In SSc a significantly low frequency of KIR2DL1 (78% vs. 92%, p=0.05) 2. In PSS a significantly high frequency of KIR2DS2 without KIR2DL2 (15.71% vs 4.9%, p=0.01). 3. No significant differences were found in the SLE group. Conclusion. This study shows that KIRs have a role in certain, but not all, systemic autoimmune diesease. These three diseases have overlapping clinical features as well as other common genetic features (preponderance of females, HLA-A1,B8,DR3). Despite this the KIR associations for these three diseases are clearly different. |
Author | Lowe, D P Welsh, KI Bowman, S J Lagan, AL Cook, MA Briggs, D C |
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