Gleeson Maree, Clancy Robert L, Cox Amanda J, Gulliver Sally A, Hall Sharron T, Cooper David M
Immunology Unit, Hunter Area Pathology Service, John Hunter Hospital, Locked Bag #1, Hunter Region Mail Centre, NSW 2310, Australia.
FEMS Immunol Med Microbiol. 2004 Sep 1;42(1):105-18. doi: 10.1016/j.femsim.2004.06.019.
This study examined the hypothesis that dysregulation of mucosal immune responses to respiratory infections is a critical event, which could be causal in respiratory arrest of some previously healthy infants. To examine this hypothesis, a prospective study was undertaken of infants presenting to the emergency department of a major teaching hospital with acute life threatening events (ALTE) of unknown cause and classified as "near-miss" SIDS. Salivary immunoglobulin concentrations were measured on admission and again after 14 days. The salivary immunoglobulins were compared with three control groups: infants with a mild upper respiratory tract infection (URTI); bronchiolitis; and healthy age-matched infants. The salivary IgA and IgM concentrations in the ALTE infants at presentation to hospital indicated a significant mucosal immune response had already occurred, with nearly 60% of the IgA concentrations significantly above the population-based reference ranges. The hyper-immune response was most evident in the ALTE infants with pathology evidence of an infection; 87% of these infants had salivary IgA concentrations on average 10 times higher that the age-related median concentration. The most prevalent pathogen identified in the ALTE infants was respiratory syncytial virus (RSV) (64%). RSV was also identified in all subjects with bronchiolitis. Risk factors for SIDS were assessed in each group. The data indicated that the ALTE infants diagnosed as 'near-miss' SIDS were a relatively homogeneous group, and most likely these ALTE infants and SIDS represent associated clinical outcomes. The study identified exposure to cigarette smoke and elevated salivary IgA concentrations as predictors of an ALTE. The study findings support the hypothesis of mucosal immune dysregulation in response to a respiratory infection in some infants with an ALTE. They provide a plausible explanation for certain SIDS risk factors. The underlying patho-physiological mechanism of proinflammatory responses to infections during a critical developmental period might be a critical factor in infants who have life-threatening apnoea or succumb to SIDS. The study raises the possibility of using salivary IgA to test infants who present with mild respiratory infections to identify a substantial number of infants at risk of developing an ALTE or SIDS, thus enabling intervention management to prevent such outcomes.
本研究检验了这样一种假设，即对呼吸道感染的黏膜免疫反应失调是一个关键事件，可能是一些此前健康的婴儿发生呼吸骤停的原因。为检验这一假设，对一家大型教学医院急诊科收治的、出现原因不明的急性危及生命事件（ALTE）且被归类为“近窒息性”婴儿猝死综合征（SIDS）的婴儿进行了一项前瞻性研究。入院时及14天后测量唾液免疫球蛋白浓度。将唾液免疫球蛋白与三个对照组进行比较：患有轻度上呼吸道感染（URTI）的婴儿；患细支气管炎的婴儿；以及年龄匹配的健康婴儿。ALTE婴儿入院时唾液中的IgA和IgM浓度表明已经发生了显著的黏膜免疫反应，近60%的IgA浓度显著高于基于人群的参考范围。这种高免疫反应在有感染病理证据的ALTE婴儿中最为明显；这些婴儿中有87%的唾液IgA浓度平均比年龄相关的中位数浓度高10倍。在ALTE婴儿中鉴定出的最常见病原体是呼吸道合胞病毒（RSV）（64%）。在所有患细支气管炎的受试者中也鉴定出了RSV。对每组中的SIDS风险因素进行了评估。数据表明，被诊断为“近窒息性”SIDS的ALTE婴儿是一个相对同质的群体，很可能这些ALTE婴儿和SIDS代表了相关的临床结局。该研究确定接触香烟烟雾和唾液IgA浓度升高是ALTE的预测因素。研究结果支持了一些患有ALTE的婴儿在呼吸道感染时黏膜免疫失调的假设。它们为某些SIDS风险因素提供了一个合理的解释。在关键发育阶段对感染的促炎反应的潜在病理生理机制可能是患有危及生命的呼吸暂停或死于SIDS的婴儿的一个关键因素。该研究提出了利用唾液IgA检测患有轻度呼吸道感染的婴儿，以识别大量有发生ALTE或SIDS风险的婴儿的可能性，从而能够进行干预管理以预防此类结局。
