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Killer Cell Immunoglobulin-like Receptor Variants Are Associated with Protection from Symptoms Associated with More Severe Course in Parkinson Disease.

ABSTRACT: Immune dysfunction plays a role in the development of Parkinson disease (PD). NK cells regulate immune functions and are modulated by killer cell immunoglobulin-like receptors (KIR). KIR are expressed on the surface of NK cells and interact with HLA class I ligands on the surface of all nucleated cells. We investigated KIR-allelic polymorphism to interrogate the role of NK cells in PD. We sequenced KIR genes from 1314 PD patients and 1978 controls using next-generation methods and identified KIR genotypes using custom bioinformatics. We examined associations of KIR with PD susceptibility and disease features, including age at disease onset and clinical symptoms. We identified two KIR3DL1 alleles encoding highly expressed inhibitory receptors associated with protection from PD clinical features in the presence of their cognate ligand: KIR3DL1*015/HLA-Bw4 from rigidity (p _c = 0.02, odds ratio [OR] = 0.39, 95% confidence interval [CI] 0.23-0.69) and KIR3DL1*002/HLA-Bw4i from gait difficulties (p _c = 0.05, OR = 0.62, 95% CI 0.44-0.88), as well as composite symptoms associated with more severe disease. We also developed a KIR3DL1/HLA interaction strength metric and found that weak KIR3DL1/HLA interactions were associated with rigidity (p_c = 0.05, OR = 9.73, 95% CI 2.13-172.5). Highly expressed KIR3DL1 variants protect against more debilitating symptoms of PD, strongly implying a role of NK cells in PD progression and manifestation.

SUBMITTER: Anderson KM

PROVIDER: S-EPMC7484130 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Killer Cell Immunoglobulin-like Receptor Variants Are Associated with Protection from Symptoms Associated with More Severe Course in Parkinson Disease.

Anderson Kirsten M KM Augusto Danillo G DG Dandekar Ravi R Shams Hengameh H Zhao Chao C Yusufali Tasneem T Montero-Martín Gonzalo G Marin Wesley M WM Nemat-Gorgani Neda N Creary Lisa E LE Caillier Stacy S Mofrad Mohammad R K MRK Parham Peter P Fernández-Viña Marcelo M Oksenberg Jorge R JR Norman Paul J PJ Hollenbach Jill A JA

Journal of immunology (Baltimore, Md. : 1950) 20200724 5

Immune dysfunction plays a role in the development of Parkinson disease (PD). NK cells regulate immune functions and are modulated by killer cell immunoglobulin-like receptors (KIR). KIR are expressed on the surface of NK cells and interact with HLA class I ligands on the surface of all nucleated cells. We investigated <i>KIR</i>-allelic polymorphism to interrogate the role of NK cells in PD. We sequenced <i>KIR</i> genes from 1314 PD patients and 1978 controls using next-generation methods and ...[more]

PMID: 32709660

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Project description:ObjectiveTo investigate the relationship between sleep disturbance, fatigue, and urinary incontinence (UI) and overactive bladder (OAB) symptoms among patients with OAB.MethodsPatients who were diagnosed with OAB and age-matched control subjects without OAB were enrolled. Sleep disturbance and fatigue symptoms were assessed using the Patient-Reported Outcomes Measurement Information System (PROMIS) short forms. UI and OAB symptoms were assessed using the International Consultation on Incontinence Questionnaire-Urinary Incontinence (ICIQ-UI), the International Consultation on Incontinence Questionnaire-Overactive Bladder (ICIQ-OAB), the Overactive Bladder Questionnaire (OAB-q), the Urogenital Distress Inventory Short Form (UDI-6), and the Incontinence Impact Questionnaire Short Form (IIQ-7). Psychosocial health (depression, anxiety, and perceived stress level) was also assessed.ResultsPatients with OAB reported a significantly greater sleep disturbance compared with controls (PROMIS 8b T-scores: 54.3 ± 10.3 vs 43.8 ± 9.2). Patients with OAB also reported a significantly greater fatigue compared with controls (PROMIS 7a T-scores: 54.7 ± 9.6 vs 46.0 ± 6.4). After adjusting for nocturia, the differences in sleep disturbance between OAB and controls became insignificant (P = .21), whereas the differences in fatigue between OAB and controls remained significant (P = .014). Among patients with OAB, there were positive correlations between sleep disturbance and the severity of OAB symptoms (ICIQ-OAB), poorer health-related quality of life (OAB-q QOL), the severity of UI symptoms (ICIQ-UI), greater incontinence impact (IIQ-7), and urinary bother (UDI-6). Positive correlations were also observed between fatigue and worse UI and OAB symptoms and quality of life. Both sleep disturbance and fatigue were associated with poor psychosocial health (depression, anxiety, and higher stress level) among patients with OAB.ConclusionSleep disturbance and fatigue are present in substantial percentages of patients with OAB. Among patients with OAB, sleep disturbance and fatigue were associated with more severe UI and OAB symptoms, worse health-related quality of life, and poorer psychosocial health.

Dataset Information

Killer Cell Immunoglobulin-like Receptor Variants Are Associated with Protection from Symptoms Associated with More Severe Course in Parkinson Disease.

Publications

Killer Cell Immunoglobulin-like Receptor Variants Are Associated with Protection from Symptoms Associated with More Severe Course in Parkinson Disease.

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