Sung Alexander P, Tang Jennifer J-J, Guglielmo Michael J, Smith-Gagen Julie, Bateman Lucinda, Navarrete-Galvan Lydia, Redelman Doug D, Hudig Dorothy
Department of Microbiology and Immunology, MS 0320, University of Nevada, Reno School of Medicine, Reno, NV 89557.
University of Nevada, Reno Health Sciences, Reno NV 89557.
Fatigue. 2020;8(4):226-244. doi: 10.1080/21641846.2021.1876613. Epub 2021 Feb 2.
Chronic fatigue syndrome (CFS) is an illness of unknown origin that may have familial risks. Low natural killer (NK) lymphocyte activity was proposed as a risk for familial CFS in 1998. Since then, there have been many studies of NK lymphocytes in CFS in general populations but few in familial CFS. Antibody-dependent cell-mediated cytotoxicity (ADCC) by NK lymphocytes helps control viral infections. ADCC is affected by variant CD16A receptors for antibody that are genetically encoded by .
This report characterizes ADCC effector NK cell numbers, ADCC activities, and variants of five families each with 2-5 CFS patients, their family members without CFS and unrelated controls. The patients met the Fukuda diagnostic criteria. We determined: CD16Apositive blood NK cell counts; EC50s for NK cell recognition of antibody; ADCC lytic capacity; alleles encoding CD16A variants, ROC tests for biomarkers, and synergistic risks.
CFS patients their family members had fewer CD16Apositive NK cells, required more antibody, and had ADCC that was lower than the unrelated controls. CFS family members were predominantly genetically CD16A F/F s for the variant with low affinity for antibodies. ROC tests indicated unsuitability of ADCC as a biomarker for CFS because of the low ADCC of family members without CFS. Familial synergistic risk controls was evident for the combination of CD16Apositive NK cell counts with ADCC capacity.
low ADCC may be a risk factor for familial CFS. Furthermore, characterization of familial CFS represents an opportunity to identify pathogenic mechanisms of CFS.
慢性疲劳综合征（CFS）是一种病因不明的疾病，可能存在家族风险。1998年有人提出自然杀伤（NK）淋巴细胞活性低是家族性CFS的一个风险因素。从那时起，针对普通人群中CFS患者的NK淋巴细胞进行了许多研究，但针对家族性CFS患者的研究较少。NK淋巴细胞介导的抗体依赖性细胞毒性（ADCC）有助于控制病毒感染。ADCC受抗体的CD16A受体变体影响，这些变体由基因编码。
本报告描述了五个家庭的ADCC效应NK细胞数量、ADCC活性及变体特征，每个家庭有2至5名CFS患者、无CFS的家庭成员及无关对照。患者符合福田诊断标准。我们测定了：CD16A阳性血液NK细胞计数；NK细胞识别抗体的半数有效浓度（EC50）；ADCC裂解能力；编码CD16A变体的等位基因、生物标志物的ROC检验以及协同风险。
CFS患者及其家庭成员的CD16A阳性NK细胞数量较少，需要更多抗体，且ADCC低于无关对照。CFS家庭成员在基因上主要是对抗体亲和力低的CD16A F/F变体。ROC检验表明，由于无CFS家庭成员的ADCC较低，ADCC不适合作为CFS的生物标志物。CD16A阳性NK细胞计数与ADCC能力相结合时，家族协同风险与对照明显不同。
低ADCC可能是家族性CFS的一个风险因素。此外，对家族性CFS的特征描述为识别CFS的致病机制提供了机会。
