Xu Xinling, Rahbar Afsar, Omarsdottir Soley, Teng Jonas, Németh Antal, Fischler Björn, Söderberg-Nauclér Cecilia
*Department of Medicine Solna, Experimental Cardiovascular Research Unit, Center for Molecular Medicine, Karolinska Institutet †Department of Rheumatology ‡Division of Pediatrics, CLINTEC, Karolinska Institutet, Astrid Lindgren Children's Hospital, Karolinska University Hospital, Stockholm, Sweden.
J Pediatr Gastroenterol Nutr. 2017 Jan;64(1):76-82. doi: 10.1097/MPG.0000000000001266.
Human cytomegalovirus (HCMV) infection induces production of CD13-specific autoantibodies, which may promote inflammation and tissue damage. HCMV infection has been suggested as a cause of biliary atresia (BA), but little is known of its role in other forms of neonatal cholestasis. We studied serum levels of CD13-specific autoantibodies in mothers of infants with neonatal cholestasis of different causes, including BA, and in mothers of healthy, term infants without cholestasis, as well as in healthy blood donors.
Using fluorescence-activated cell sorting, we measured CD13-specific autoantibody levels in serum from the above-mentioned groups. In addition, the effect of serum from mothers of infants with neonatal cholestasis was tested on the differentiation of monocytes into macrophages.
CD13-specific autoantibodies were found in mothers of infants with neonatal cholestasis, but not in mothers of infants without cholestasis and healthy blood donors, and were associated with HCMV seropositivity. Sera from mothers of infants with all forms of neonatal cholestasis inhibited differentiation of monocytes into macrophages, but this was not dependent on CD13-specific autoantibodies.
The significantly higher frequency of CD13-specific autoantibodies in mothers of infants with neonatal cholestasis of all forms compared with mothers of healthy infants without cholestasis suggests an association, but does not prove that they are pathogenic. The presence of CD13-specific autoantibodies does not correlate with HCMV IgG serostatus, suggesting a more complicated mechanism that possibly reflects active HCMV infection in these individuals. Further studies are needed to elucidate whether these autoantibodies contribute to the development of cholestasis or represent an epiphenomenon.
人巨细胞病毒(HCMV)感染可诱导产生CD13特异性自身抗体,这可能会促进炎症和组织损伤。HCMV感染被认为是胆道闭锁(BA)的一个病因,但对其在其他形式的新生儿胆汁淤积症中的作用知之甚少。我们研究了不同病因(包括BA)的新生儿胆汁淤积症患儿母亲、无胆汁淤积症的足月健康婴儿母亲以及健康献血者血清中CD13特异性自身抗体的水平。
我们使用荧光激活细胞分选技术测量上述各组血清中CD13特异性自身抗体的水平。此外,还检测了新生儿胆汁淤积症患儿母亲血清对单核细胞向巨噬细胞分化的影响。
在新生儿胆汁淤积症患儿母亲中发现了CD13特异性自身抗体,而在无胆汁淤积症患儿母亲和健康献血者中未发现,且与HCMV血清阳性有关。所有形式新生儿胆汁淤积症患儿母亲的血清均抑制单核细胞向巨噬细胞的分化,但这并不依赖于CD13特异性自身抗体。
与无胆汁淤积症的健康婴儿母亲相比,所有形式新生儿胆汁淤积症患儿母亲中CD13特异性自身抗体的频率显著更高,这表明存在关联,但并未证明它们具有致病性。CD13特异性自身抗体的存在与HCMV IgG血清状态无关,提示存在更复杂的机制,这可能反映了这些个体中活跃的HCMV感染。需要进一步研究以阐明这些自身抗体是否有助于胆汁淤积症的发展或只是一种附带现象。