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Objective: To analyze the clinical features and the results of the whole exome sequencing (WES) of a Chinese family containing both pulmonary sarcoidosis patients and healthy members, and to find potent genes and variants that may be involved in the pathogenesis of sarcoidosis. Methods: Three patients with pulmonary sarcoidosis and 1 healthy member was included from a Chinese Han family in the north of China diagnosed in November 2016, which characterized as 2 consecutive generations including 2 males and 1 female, aged from 23 to 69 years old. The proband is Ⅱ-6. Pulmonary sarcoidosis was diagnosed by clinical features, imaging and pathological findings, and clinical data such as family history were collected. Whole blood samples were taken and WES (Illumina NovaSeq S2) was performed. The pathogenicity analysis and gene annotation analysis were performed by ExAC, SIFT, Polyphenv2, Metascape databases. Results: It was found that 27 genes were highly pathogenic in the database filtering result. After gene annotation analysis, we found that ZC3H12A gene can negatively regulate the differentiation of Th17 cells, which may be involved in the onset of pulmonary sarcoidosis. Sanger sequencing confirmed the c.1361 A>G variant in 3 sarcoidosis patients but normal in healthy member. Conclusions: In patients with familial pulmonary sarcoidosis, the genetic background could regulate immune response which is one of the pathogenic mechanisms of sarcoidosis. The whole exome test and gene ontology analysis showed that Ⅱ-2, Ⅱ-6 and Ⅲ-1 pulmonary sarcoidosis patients in this family were all shared the same variant on ZC3H12A gene, which played a pivotal role in differentiation of Th17 cells and is a potent pathogenesis gene in this Chinese pulmonary sarcoidosis family.

Objective: To explore the role of histone deacetylases(HDAC) in the pathogenesis of idiopathic pulmonary fibrosis(IPF) and cryptogenic organizing pneumonia(COP). Methods: Fifteen IPF patients [14 males and 1female, age 40-73 years, mean age (59±8) years] and 15 COP patients [5 males and 10 females, age 41-71 years, mean age (59±8) years] from Peking Union Medical College Hospital were recruited from March 2018 to October 2018. Fifteen healthy donors[4 males and 11females, age 43-70 years, mean age (58±6) years] were enrolled as controls. Peripheral blood mononuclear cells (PBMC) were isolated by density gradient centrifugation. The nuclear and cytoplasmic proteins were extracted by Nuclear Extraction Kit. HDAC activity was measured by fluorimetric method. The relations between HDAC activity and clinical parameters were analyzed with SPSS. Results: The HDAC activity of cytoplasmic protein and nuclear protein from patients with IPF were (724±216) nmol/L and (2 309±708) nmol/L, which were higher than that of health controls (409±105) nmol/L and (1 572±611) nmol/L ( P< 0.01 for both). So as to the HDAC activity of cytoplasmic protein and nuclear protein from patients with COP which were (718±245) nmol/L and (3 310±1 005) nmol/L ( P< 0.01 for both).The HDAC activity of nuclear protein from COP patients was higher than that from IPF patients ( Z= -2.840, P= 0.005). The HDAC activity of nuclear protein was negatively correlated with FEV(1) and D(L)CO in IPF patients ( r= -0.574, P= 0.025; r= -0.583, P= 0.029), and negatively correlated with FVC and TLC in COP patients( r= -0.846, P= 0.016; r= -0.900, P= 0.015). Conclusion: HDAC may be involved in the pathogenesis of COP and IPF.

Objective: To explore the differential diagnostic role of B cell-activating factor(BAFF) in idiopathic pulmonary fibrosis (IPF) and usual interstitial pneumonia (UIP) associated with autoimmune diseases (AIDs). Methods: Plasma levels of BAFF were measured by ELISA method in 23 patients with AIDs-UIP, 34 patients with IPF, and 21 healthy subjects as control. The correlation between plasma BAFF levels and other clinical results from patients was analyzed. Receiver operating characteristics (ROC) analysis for distinguishing AIDs-UIP from IPF patients was examined and the maximal area under curve (AUC) was found. Results: Plasma levels of BAFF were significantly elevated in AIDs-UIP patients and IPF patients compared to healthy subjects( P <0.001 and P =0.002, respectively). AIDs-UIP patients had higher level of BAFF than IPF patients( P =0.030). Plasma BAFF levels in AIDs-UIP patients were inversely correlated with pulmonary function results, including FVC%( r =-0.435, P =0.040)and TLC%( r =-0.449, P =0.041), as well as DLCO%( r =-0.491, P =0.024). When the cut off value of BAFF was set as 1.5 ng/ml to distinguish AIDs-UIP patients from IPF patients, the sensitivity and the specificity was 64.5% and 90.0%, respectively, and the area under ROC curve reached the maximum of 0.784( P =0.000, 95% CI: 66.3%-90.5%). Conclusions: Plasma BAFF levels were significantly higher and inversely correlated with pulmonary function, reflecting the severity of AIDs-UIP patients. Plasma BAFF levels may be a useful marker for distinguishing AIDs-UIP from IPF.

Fifty-six cases with lung carcinoma were detected for peripheral blood T lymphocyte by direct staphylococcal protein A (SPA) bacterial rose ring for carcino-embryonic antigen (CEA) by radioimmunoassay, and the relationship between T lymphocyte. CEA and Syndrome of TCM was explored. The results were as follows:the values of OKT3, OKT4, OKT4/OKT8 were lower in the lung carcinoma than that in healthy subjects (P < 0.05-0.01), but OKT8 was higher (P < 0.05); The values of T lymphocyte lowered or increased in the order of Yin Deficiency with internal Heat, Qi Stagnation with blood stasis, Phlegm-Dampness in Lung, Qi-Yin Deficiency, but that of CEA was the highest in Qi-stagnation with blood stasis. There was a significant difference between all Syndrome-types of TCM and the healthy subjects (P < 0.01). Therefore, it is suggested that the values of peripheral T lymphocytes and CEA with the lung carcinoma were regarded as good referential parameters in reflection the condition of Deficiency in Vitality and Excess in Superficiality, which offered the objective evidence for the TCM treatment.