Zdziarski Przemyslaw, Gamian Andrzej, Dworacki Grzegorz
Department of Clinical Immunology, Lower Silesian Center for Cellular Transplantation L Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw Department of Immunology, Poznan University of Medical Sciences, Poznań, Poland.
Medicine (Baltimore). 2017 Jun;96(23):e7031. doi: 10.1097/MD.0000000000007031.
Lymphoid interstitial pneumonia (LIP) is a rare disease with lymphocytic infiltration of the alveolar interstitial and air spaces, sometimes classified as a clonal lymphoproliferative disease (LPD) with high prevalence in patients with immunodysregulation. Although association of mucosa-associated lymphoid tissue (MALT) lymphoma development with infectious agents has been well described, it is not so in the case of LIP. Attempts to demonstrate an infective cause by direct microbe detection have failed, but association with atypical specific immune response to opportunistic infectious agent has not been studied.
We performed clinical, biochemical, and immunologic analysis of patients LIP that arises primarily from the common variable immune deficiency (CVID) with normal immunoglobulin class M (IgM) level and mild infectious course as a result of immunodysregulation. At the age of 13 multiple nodules, areas of consolidation were observed and LIP was confirmed by histological examination. The progression of the disease with massive splenomegaly (17→27 cm), lymphadenopathy soft tissue infiltration coincides with high standardized uptake value (SUV was 3.1-5.2), regulatory T cells decrease (CD4+25FoxP3+ level -0.02%, i.e., 8 cells per 100 μL), oligoclonal gammapathy: very high IgM (3340 mg/dL) and β2-microglobulin (18.8 mg/L) level observed 10 years later.Immune response polarization was observed in humoral and cellular compartment -Th and Tc-dependent: 10.8% of lymphocytes are CD8high+CMV pp65-pentamer positive cells (Epstein-Barr virus-specific not observed). Specific immune response polarization correlates with negative immunofixation, light chains κ/λ = 2.84 and narrow, but non-monoclonal T cell receptor (TCR)/ B cell receptor (BCR) repertoire.
Taking everything into account, this case report shows that LIP is a consequence of immune-dysregulation in CVID, that is, Treg deficiency, narrow lymphocyte repertoire, and abnormal ability to respond to cytomegalovirus (CMV) antigens. It may be visualized by positron emission tomography (PET) and monitored by CMV-specific immune response, β2-microglobulin level, and IgM paraproteinaemia, but not by immunofixation and κ/λ ratio.
淋巴样间质性肺炎（LIP）是一种罕见疾病，其特征为肺泡间质和肺泡腔出现淋巴细胞浸润，有时被归类为一种克隆性淋巴细胞增殖性疾病（LPD），在免疫调节异常的患者中患病率较高。虽然黏膜相关淋巴组织（MALT）淋巴瘤的发生与感染因子的关联已得到充分描述，但LIP的情况并非如此。通过直接检测微生物来证明感染病因的尝试均告失败，但与对机会性感染因子的非典型特异性免疫反应的关联尚未得到研究。
我们对主要由常见可变免疫缺陷（CVID）引起的LIP患者进行了临床、生化和免疫学分析，这些患者免疫球蛋白M（IgM）水平正常，因免疫调节异常而具有轻度感染病程。13岁时观察到多个结节及实变区域，经组织学检查确诊为LIP。疾病进展伴有巨大脾肿大（17→27厘米）、淋巴结病及软组织浸润，同时标准化摄取值较高（SUV为3.1 - 5.2）、调节性T细胞减少（CD4 + 25FoxP3 + 水平为0.02%，即每100微升8个细胞）、寡克隆丙种球蛋白病：10年后观察到非常高的IgM（3340毫克/分升）和β2微球蛋白（18.8毫克/升）水平。在体液和细胞区室观察到免疫反应极化——Th和Tc依赖性：10.8%的淋巴细胞是CD8高 + CMV pp65 - 五聚体阳性细胞（未观察到爱泼斯坦 - 巴尔病毒特异性）。特异性免疫反应极化与阴性免疫固定、轻链κ/λ = 2.84以及狭窄但非单克隆的T细胞受体（TCR）/B细胞受体（BCR）库相关。
综合考虑所有因素，本病例报告表明LIP是CVID中免疫调节异常的结果，即调节性T细胞缺乏、淋巴细胞库狭窄以及对巨细胞病毒（CMV）抗原的异常反应能力。它可以通过正电子发射断层扫描（PET）可视化，并通过CMV特异性免疫反应、β2微球蛋白水平和IgM副蛋白血症进行监测，但不能通过免疫固定和κ/λ比值进行监测。
