Predominant T helper 1 cells in patients with idiopathic portal hypertension

BACKGROUND: The pathologic mechanism of idiopathic portal hypertension (IPH) is unknown. Because cytokines and the balance of T helper (h) 1 and Th2 CD4+ T cells have been reported to be important for regulating the immune response, in the present study we investigated the role of cytokines and the distribution of cytokine-producing cells in IPH patients. METHODS: Serum levels of tumor necrosis factor (TNF)-alpha, soluble TNF receptor-I, -II, interferon (IFN)-gamma and interleukin (IL)-4 were measured in IPH patients, fatty liver patients, chronic hepatitis patients and control subjects. The percentages of Th0, Th1 and Th2 CD4+ T cells were examined in peripheral and spleen lymphocytes in IPH patients by intracellular staining. RESULTS: Serum levels of TNF-alpha, soluble TNF receptor-I, interferon-gamma and IL-4 of IPH patients were not increased in comparison with control subjects. Only the mean value of soluble TNF receptor-II was significantly higher than that of control subjects and fatty liver patients. The ratios of Th1 and Th2 in both peripheral and spleen lymphocytes of IPH patients were significantly increased compared with the ratios found in peripheral lymphocytes of control subjects. The increase in the ratios was due to a decrease in the percentage of Th2 CD4+ T cells. CONCLUSIONS: These results suggest that the imbalance of Th1 and Th2 CD4+ T cells and TNF may be associated with the pathogenesis of IPH.     

Determination of sub-populations of circulating T lymphocytes in alcoholic cirrhosis using monoclonal antibodies OKT3, 4, 5, Leu 2 and Leu 15. Effect of hepatitis B virus infection

Peripheral T lymphocyte subpopulations were quantified in 24 alcoholic cirrhotic patients, 11 of them having anti-HBs and/or anti-HBc antibodies, and were compared with 35 healthy control subjects, 10 of them having anti-HBs and/or anti-HBc antibodies. The monoclonal antibodies utilized (OKT3, OKT4, OKT8 in simple staining, Leu 2 and Leu 15 in double staining) are considered as markers of mature (CD3), helper (CD4), cytotoxic/suppressor (CD8, Leu 2), suppressor (Leu [2+ 15+), and cytotoxic (Leu 2+ 15-) T cells. In cirrhotics, when compared to controls, the number of CD3 cells was reduced (p less than 0.01); the proportion of CD4 cells was within normal range, and that of CD8 cells diminished (p less than 0.001), contrasting with an increased proportion of Leu 2+ cells (p less than 0.01), related to an increased proportion of Leu 2+ 15+ cells. Leu 2+ 15- lymphocytes were within normal range. In control subjects, a decreased proportion of Leu 2+ 15+ cells was found (p less than 0.05) when Ac HBs and/or Ac HBc were present. In cirrhotics having at least one serologic marker of hepatitis B virus infection, when compared with negative ones, increased proportions of Leu 2+ (p less than 0.05) and Leu 2+ 15+ (p less than 0.05) cells were found. These results show that data concerning T lymphocyte subpopulations are conflicting when various types of antibodies are used. However, they suggest abnormalities of immune regulation, possibly a defect of T suppressor cell function. Hepatitis B virus infection probably modifies immune regulation in alcoholic cirrhosis, and perhaps in normal subjects.     

Phenotype study of blood T lymphocytes in alcoholic hepatopathies

Peripheral blood T lymphocytes and T lymphocytes subsets have been quantified by an indirect immunofluorescence technique using monoclonal antibodies, in 10 patients with fatty liver, 8 with acute alcoholic hepatitis (AAH), 10 with inactive cirrhosis and 7 with cirrhosis and AAH. Twenty normal subjects were studied as controls. As compared to controls (1.81 +/- 0.56 10(9)/l), we found a reduced number of peripheral T lymphocytes (OKT3+) in patients with inactive cirrhosis (0.98 +/- 0.45, p less than 0.001) and in patients with cirrhosis and AAH (1.22 +/- 0.51, p less than 0.02). The OKT4 to OKT8 ratio was normal in patients with fatty liver or inactive cirrhosis, but it was significantly higher in patients with AAH with or without cirrhosis (2.83 +/- 0.79, p less than 0.01, and 2.10 +/- 0.56, p less than 0,02, respectively) than in controls (1.68 +/- 0.24). In both groups, this increased ratio was due to a decreased proportion of OKT8+ circulating lymphocytes (19.2 +/- 6.7 p. 100, p less than 0.01, and 21.8 +/- 4.6 p. 100, p less than 0.02, respectively) when compared to controls (27.1 +/- 4.1 p. 100). The T-cell imbalance observed in patients with liver cell necrosis may be of importance in the pathogenesis of alcoholic liver disease.     

Expression of NK-lineage markers on peripheral blood lymphocytes with T- helper (Leu3+/T4+) phenotype in B cell chronic lymphocytic leukemia

Heterogeneity within lymphocyte subsets expressing T-helper (T4+/Leu3+) or T-suppressor (T8+/Leu2+) markers was analyzed in 38 patients with B cell chronic lymphocytic leukemia (B-CLL) and in 11 age-matched controls. Co-expression of NK-lineage markers (M1, Leu7) on Leu2+ or Leu3+ cells was investigated by two-color immunofluorescence, and the proportion of granular lymphocytes within each subset was determined by cytochemical staining for acid phosphatase. B-CLL patients and normal controls had similar absolute numbers of cells per microL with T- suppressor phenotype. However, the proportion of Leu2+ cells co- expressing the Leu7 antigen was higher in the B-CLL patients than in the control subjects (54 +/- 3% v 27 +/- 4%, P less than .0001). The absolute number per microL of cells with T-helper phenotype was somewhat decreased in B-CLL patients compared with normal subjects (649 +/- 104 v 799 +/- 33, P less than .02), with a consequent decrease of the helper/suppressor ratio. Furthermore, co-expression of the Leu7 and, more strikingly, of the M1 markers was increased significantly on Leu3+ cells from B-CLL patients compared with normal controls (11 +/- 2% v 2 +/- 0.7%, P less than .002 for Leu7 and 40 +/- 5% v 4 +/- 1%, P less than .00001 for M1). Cytochemical studies showed that a large proportion of Leu3+ cells from B-CLL patients were granular lymphocytes, as suggested by the co-expression of natural killer (NK) cell markers. The emergence of a population of Leu3+ granular lymphocytes with NK markers, which is barely detectable in normal subjects, may provide an explanation for the impairment of T cell functions repeatedly described in B-CLL.     

Significance of Enhanced Expression of Nitric Oxide Syntheses in Splenic Sinus Lining Cells in Altered Portal Hemodynamics of Idiopathic Portal Hypertension

Idiopathic portal hypertension (IPH) is characterized by noncirrhotic portal hypertension due mainly to increased intrahepatic, presinusoidal resistance to portal blood flow. Marked splenomegaly is always seen in IPH. To clarify the pathogenetic significance of splenomegaly, immunohistochemical expression of inducible nitric oxide synthese (iNOS), endothelial NOS (eNOS), and endothelin-1 (ET-1) in spleens from patients with IPH was examined. Sinus lining cells of IPH spleens showed diffuse and strong expression of iNOS and eNOS. Sinus lining cells of spleens from patients with liver cirrhosis (LC) also showed positive signals for iNOS and eNOS, but the staining intensity was significantly weak. ET-1 was detectable in only a few mononuclear leukocytes in the red pulp of both IPH and LC spleens. These results suggest that NO liberated in spleen, rather than ET-1, is responsible for the dilatation of splenic sinuses, leading to splenomegaly, and thereby contributes to portal hypertension in IPH.     

Monoclonal antibody-defined T-cell subsets in hairy-cell leukaemia

In 17 tests in 14 patients with hairy-cell leukaemia (HCL), peripheral blood Leu 2a+ and 3a+ suppressor and helper cells were present in normal mean percentage (3a+ 63 +/- 15%, normal 64 +/- 8%; 2a+ 39 +/- 16%, normal 34 +/- 8%), absolute (3a+ 0.8 +/- 0.4 x 10(9)/1, normal 0.6-1.4 x 10(9)/1; 2a+ 0.5 +/- 0.4 x 10(9)/1, normal 0.2-0.6 x 10(9)/1), and relative (3a+/2a+) (2.2 +/- 1.3, normal 1.9 +/- 0.7) numbers. In all the 9 untreated patients, 3a+ helper cells were normal or increased in percentage numbers, while 2a+ suppressor cells were normal or slightly reduced. It is suggested that these data explain, at least in part, the lack of immuneparesis of HCL as compared with chronic lymphocytic leukaemia (CLL) which is consistently associated with immuneparesis and an excess of Leu 2a+ suppressor cells. In individual splenectomised patients, some variations in Leu 2a+ and 3a+ numbers were observed, and it is suggested that the spleen, known to be important in the natural history of HCL, may have an influence on peripheral T-cell subsets. Although HCL is clearly shown to differ from CLL and myeloma regarding T-cell subset numbers, the fundamental mechanism underlying this difference remains unknown.     

Immunological features of nonimmunogenic hyperthyroidism

Blood lymphocyte subpopulations (Leu 4+ cells = pan-T cells, Leu 3a+ cells = helper/inducer cells, and Leu 2a+ cells = suppressor/cytotoxic cells), thyroid-stimulating immunoglobulins, microsomal antibodies and antibodies against thyroglobulin were determined in 10 patients with hyperthyroidism due to single autonomously functioning thyroid nodules (ATN), 11 patients with hyperthyroidism due to Graves' disease (GD) and in 20 normal subjects. Thyroidectomy was performed in 8 of the patients with ATN and in 6 of those with GD after 3 weeks of antithyroid drug treatment with methimazole. Lymphocytic infiltration of thyroid tissue, the amount of the various lymphocyte subsets (Leu 4+, Leu 3a+, and Leu 2a+ T cells as well as B+ B cells) in the thyroid gland, as well as the expression of the histocompatibility antigen HLA-DR on thyrocytes and intrathyroidal lymphocytes were examined. Blood Leu 4+ cells were reduced due to a lack of Leu 2a+ cells in patients with ATN and GD when compared to normal subjects. Thyroid-stimulating immunoglobulins were detected in all patients with ATN and GD, but in none of the normal subjects. Lymphocytic infiltration of thyroid tissue was present in patients with ATN and GD. The various lymphocyte subsets in the thyroid gland did not differ between the two patient groups. DR expression on thyrocytes was seen in 6 of the patients operated for ATN and in 5 of those who underwent surgery for GD. Infiltration with DR+-T lymphocytes was found in all thyroid glands investigated. Thus immunological findings usually classified as proof for the autoimmune origin of GD exist also in patients with ATN. An overlap in the pathogenetic background of both diseases seems possible.     

Influence of HBV replication and delta agent superinfection on T cell subsets and killer (Leu 7+) in chronic hepatitis B virus infection

Peripheral blood T-lymphocyte subsets and cells reacting for Leu 7 antigen, which identifies a subset of killer and natural killer cells, have been examined in 32 patients chronically infected by the hepatitis B or D viruses (HBV, HDV) and in 28 normal subjects. The T8+ lymphocytes were increased and the T4/T8 ratio was decreased in patients with HBV replication (identified by the presence of HBcAg in liver and HBV-DNA in serum) and in patients with HDV infection (HDAg in liver). These patients had more active liver disease than patients without evidence of viral replication, B or D, who showed normal lymphocyte counts. Leu 7+ lymphocytes were also increased in patients with viral replication and active disease and correlated positively with alaninaminotransferase serum levels. These observations suggest the participation of both T8+ and Leu7+ cells in the pathogenesis of liver cell injury in HBsAg-positive chronic liver disease.     

Heterogeneity of immunoregulatory T-cell subsets in systemic lupus erythematosus. Correlation with clinical features

Immunoregulatory T-cell subsets as defined by differentiation antigens were studied in 32 patients with systemic lupus erythematosus (SLE) and 16 healthy persons using the monoclonal antibodies OKT 3 or anti-Leu 4 (T cells), anti-Leu 2a (suppressor/cytotoxic cells) and anti-Leu 3a (helper/inducer cells). Compared with the 95 percent confidence limits in control subjects, decreases or increases of Leu 3a+ cells were observed in 23 patients, whereas abnormal percentages of Leu 2a+ cells were observed in only 10 patients (p less than 0.002). The ratio of Leu 3a+ to Leu 2a+ cells varied over a much broader range (0.31 to 4.14) in patients with SLE than in control subjects (95 percent confidence limit 1.04 to 2.20). Furthermore, the helper:suppressor ratio correlated significantly (p less than 0.001) with a numerical clinical characterization of the patients. A low helper: suppressor ratio was observed in patients with severe renal disease, thrombocytopenia and onset of SLE by 20 years of age. Patients with a high helper:suppressor ratio had multisystem disease including lymphadenopathy, but only rarely SLE renal disease. Patients with a normal helper:suppressor ratio had the most widespread multisystem disease, often involving the kidneys and the central nervous system. The ratio was not correlated with duration of illness, disease activity or corticosteroid dosage in the patients examined. The study suggests that SLE is not one disease entity, but rather a symptom complex with different immunoregulatory abnormalities and associated manifestations.     

Noninvasive diagnostic method for idiopathic portal hypertension based on measurements of liver and spleen stiffness by ARFI elastography

Background

Acoustic radiation force impulse (ARFI) elastography is an ultrasound technique that is capable of measuring tissue stiffness noninvasively. It is difficult to differentiate idiopathic portal hypertension (IPH) from liver cirrhosis (LC) or chronic hepatitis (CH), and liver biopsy is essential. We investigated whether it would be possible to noninvasively diagnose IPH by measuring the stiffness of the liver and spleen by ARFI.

Methods

The subjects were 17 IPH patients, 25 LC patients, 20 CH patients, and 20 normal controls (NC). We measured liver stiffness, spleen stiffness, and the spleen/liver stiffness ratio, and plotted ROC curves.

Results

The median value of liver stiffness in the IPH group was lower than that in the LC group (p = 0.00077) and about the same as in the CH group (p = 0.79). The median value of spleen stiffness was highest in the IPH group (IPH vs. LC group, p = 0.003; IPH vs. CH group, p < 0.00001). The spleen/liver stiffness ratio was lower in the LC group and in the CH group, and higher in the IPH group (p < 0.001, respectively). When an ROC curve of spleen/liver stiffness ratios was plotted to differentiate between the IPH group and the combined group of patients with other liver diseases (LC + CH group), when a cutoff value of 1.71 was used, the AUROC was 0.933 sensitivity 0.941, specificity 0.800, and accuracy 0.839.

Conclusion

Measuring the spleen/liver stiffness ratio by ARFI made it possible to noninvasively, specifically, and accurately diagnose IPH.     

Pathomorphologic study on the extrahepatic portal vein in idiopathic portal hypertension

Patients with idiopathic portal hypertension (IPH) are known to have sclerotic changes of the intrahepatic portal vein radicles. In order to elucidate the pathological changes in the extrahepatic portal venous system in IPH, studies were carried out on the portal trunk in 12 patients with IPH, 59 patients with liver cirrhosis including some with associated hepatocellular carcinoma, and 12 normal matched control subjects. Histological examinations including histomorphometry were performed on the transverse sections of the portal trunk taken at autopsy. Most of the patients with IPH showed severe phlebosclerosis which was more pronounced than seen in liver cirrhosis. Thrombosis was also frequently observed in IPH. In IPH, the portal trunk was characterized by fibrous thickening of the intima and media with a prominent increase of elastic fibers. The mean area and thickness of the intima and media were significantly greater than in patients with liver cirrhosis. Sclerosis extensively involving both the extrahepatic and intrahepatic ramifications of the portal vein appeared to be characteristic of IPH.     

Human myeloma: several subsets of circulating lymphocytes express plasma cell-associated antigens

Peripheral blood lymphocytes from 9 monoclonal gammopathies of undetermined significance (MGUS) and 27 multiple myelomas (MM) were studied with a panel of monoclonal antibodies (MoAb) that recognize B and T lymphocytes and plasma cells. No difference in the percentage of B lymphocytes, identified by B1 and B4 MoAb, was observed in MGUS and MM patients versus normal controls. However, high percentages of circulating lymphocytes expressing plasma cell-associated antigens were detected in MM (HAN-PC1+ = 29.4 +/- 20.4%; TEC-T10+ = 27.8 +/- 19.2%) whereas they were in the normal range in MGUS (HAN-PC1+ = 8.8 +/- 5.8% p = 0.006; TEC-T10+ = 5.7 +/- 4.7% p less than 0.001). Almost identical results were obtained using PCA-1 MoAb in 17 of these patients. TEC-T10+ and PCA-1+ lymphocytes were sorted and re-analyzed with phycoerythrin conjugated MoAb in 3 healthy subjects, 2 MGUS, and 4 MM patients. In normal subjects and in MGUS the majority of PCA-1+ cells belonged to the B lineage (Leu 2-, Leu3-, Leu 15-, HLA-Dr+), whereas the majority of TEC-T10+ cells are represented by activated T cells and NK cells (Leu 15+). In MM an abnormal expansion of T lymphocytes was chiefly responsible for the high values of lymphocytes expressing plasma cell-associated antigens. Moreover, in MM a clinical evaluation showed a correlation between the presence of these lymphocytes and an aggressive disease. Indeed, they can be considered a useful prognostic marker.     

Decreased interleukin-2 receptor β chain expression by peripheral blood lymphocytes in chronic liver disease

To investigate the decrease in natural killer (NK) activity in chronic liver disease, interleukin-2 receptor beta chain (IL-2R beta) expression was assessed by peripheral blood lymphocytes (PBL) using flow cytometry and an IL-2R beta chain-specific mouse monoclonal antibody. The percentage of IL-2R beta chain-positive PBL was significantly decreased in patients with chronic viral hepatitis, liver cirrhosis and hepatocellular carcinoma in comparison with normal controls (P less than 0.01). Among chronic viral hepatitis patients, it was significantly less in those with chronic active hepatitis than in those with chronic persistent hepatitis (P less than 0.05). Two-colour flow cytometry revealed that the IL-2R beta chain was mainly expressed by CD8+ or CD16+ cells in both the controls and the liver disease patients. CD8dull+ cells (NK cells) constituted more than 60% of the CD8+ cells expressing the IL-2R beta chain. Expression of the IL-2R beta chain with CD8 or CD16 was also significantly decreased in chronic liver disease patients compared with controls. In chronic viral hepatitis, there was a significant correlation between NK activity and the percentage of IL-2R beta+ PBL (P less than 0.001, r = 0.916), as well as between NK activity and the percentage of PBL co-expressing both the IL-2R beta chain and CD16 (P less than 0.001, r = 0.850). These findings suggest that decreased expression of the IL-2R beta chain by PBL may result in diminished NK activity in chronic liver disease.     

Lymphocyte subpopulations in bronchoalveolar lavage in Sj?gren's syndrome. Evidence for an expansion of cytotoxic/suppressor subset in patients with alveolar neutrophilia

We initiated this study to determine the cellular composition and T-lymphocyte subpopulations of fluid from bronchoalveolar lavage from 15 patients with primary Sj?gren's syndrome (1SS), six patients with secondary Sj?gren's syndrome associated with primary biliary cirrhosis (2SS-PBC), eight patients with secondary Sj?gren's syndrome associated with collagen-vascular diseases (2SS-CVD), and 12 normal subjects. All were nonsmokers who were free of clinical pulmonary symptoms and had normal findings on chest roentgenograms. Lymphocyte subsets were identified by mouse monoclonal antibodies that were specific for T-cells, helper/inducer, and suppressor/cytotoxic (namely, OKT3, OKT4, and OKT8). Patients with 1SS, patients with 2SS-PBC, and patients with 2SS-CVD had a significantly increased percentage of lymphocytes in fluid from bronchoalveolar lavage (respectively, 21.6 +/- 3.7 percent, 24.3 +/- 6.1 percent, and 25.6 +/- 3.9 percent) compared with the normal value of control subjects (9.9 +/- 1.5 percent). In addition, two of the 15 patients with 1SS and five of the eight patients with 2SS-CVD demonstrated an increased percentage of alveolar neutrophils. The predominant T-cell subset in patients with 1SS was T4+, and the mean T4:T8 ratio was normal. The percentage of T4+ cells was increased in patients with 2 SS-PBC, resulting in an increased T4:T8 ratio. In contrast, patients with 2 SS-CVD demonstrated a markedly increased percentage of T8+ cells, reflected by a shift in the T4:T8 ratio which was inverted. Patients with Sj?gren's syndrome and with neutrophilia on bronchoalveolar lavage had a marked expansion of the T8+ lymphocyte subpopulation, where as patients with Sj?gren's syndrome and with pure lymphocytosis on bronchoalveolar lavage showed predominantly T4+ cells. In addition, we found a strong positive correlation between the number of neutrophils and the number of T8+ cells in bronchoalveolar lavage from patients with Sj?gren's syndrome (r = 0.74; p less than 0.05). Until the functional activities of OKT4+ and OKT8+ cells are better defined, the role that these cells play in the pathogenesis of pulmonary disease in Sj?gren's syndrome remains unclear.     

Quantitative immunological differences between newly diagnosed Graves' disease patients and relapsed patients

Class 2-positive T cells, T-cell and mononuclear cell subsets, thyrotropin receptor antibodies (TRAb) and immune complexes were evaluated in 34 newly diagnosed Graves' patients and in 13 relapsed patients before a cycle of specific medical treatment. Class II-positive T lymphocytes were detected by monoclonal antibodies against different epitopes of class II antigens, whereas 4F2-positive cells were detected by 4F2 monoclonal antibody. 4F2-positive cells were statistically increased in newly diagnosed Graves' patients compared to relapsed patients (p less than 0.05). An increased percentage of class II activated T cells, detected by monoclonal antibodies L243, was found in newly diagnosed patients in comparison with relapsed subjects (p less than 0.025). Newly diagnosed Graves' patients showed a significant decrease in the ratio suppressor/cytotoxic T cells in comparison with normal control subjects but not with relapsed patients. Ninety-one % of newly diagnosed Graves' patients showed a high TRAb value, whereas only 69% of relapsed patients showed increased values (p less than 0.025). No difference was observed in the immune complex positivity between newly diagnosed Graves' patients and relapsed subjects. In conclusion, both humoral and cellular immune differences were found in relapsed patients vs newly diagnosed Graves' patients. The immunological abnormalities are quantitatively more pronounced in the latter group.     

Suppression of immunoglobulin synthesis by lymphocyte subpopulations in patients with Crohn's disease

In previous studies, patients with mild or inactive Crohn's disease were found to have increased suppressor T-cell activity. To further characterize suppressor T cells in Crohn's disease, studies were carried out with the use of monoclonal antibodies. Excessive suppressor activity was eliminated by removal of OKT 8+ lymphocytes by complement-mediated lysis. However, the percentage of OKT 8+ (or Leu 2a+) cells and the ratio of OKT 4+ to OKT 8+ (or Leu 3a+ to Leu 2a+) cells were not significantly different from normal. Although the subgroup of patients with increased suppression of immunoglobulin synthesis had a significantly lower mean Leu 3a to Leu 2a ratio than that of normal subjects, in the whole group of Crohn's patients studied, neither the percentage of Leu 2a+ cells nor the ratio of Leu 3a+ to Leu 2a+ cells correlated with excessive suppression of immunoglobulin synthesis. A subpopulation of Leu 2a+ lymphocytes reactive with the monoclonal antibody HNK-1 (Leu 2a+ HNK-1+) was increased in patients with Crohn's disease. Furthermore, elimination of HNK-1-reactive lymphocytes by complement-mediated lysis diminished the excessive suppressor cell function in patients with Crohn's disease. The percentage of Leu 2a+ HNK-1+ lymphocytes correlated significantly with the suppression of pokeweed mitogen-stimulated immunoglobulin synthesis in vitro. Thus, patients with mild Crohn's disease have an increased suppressor cell activity in vitro which correlates with the presence of a subset of lymphocytes that have an HNK-1+ Leu-2a+ phenotype.     

Impairment of autologous mixed lymphocyte reaction in the spleen and peripheral blood lymphocytes of patients with idiopathic portal hypertension

The etiology of idiopathic portal hypertension (IPH) is unknown, although many studies have suggested that it might be an autoimmune disease. The autologous mixed lymphocyte reaction (AMLR) involves the proliferation of T lymphocytes when co-cultured with autologous non-T cells and may reflect immune control mechanisms in vivo. The AMLRs in the spleen and peripheral blood of three patients with IPH were measured and it was shown that the AMLRs both in the spleen and peripheral blood were significantly suppressed compared to those of normal healthy subjects. By allogeneic MLR, there was a tendency that the disturbance of non-T cells was more intensive than that of T cells. The AMLR of peripheral blood did not improve by splenectomy. Thus, the depressed cause of AMLR in patients with IPH was suggested mainly to disturbance of the antigen-presenting ability of non-T cells, and it was suggested that not only the spleen cells, but systemic immune disturbance caused the impairment of AMLR in IPH.     

外周血淋巴细胞亚群在慢性HBV感染过程中表达的变化分析

目的探讨HBV感染患者外周血淋巴细胞亚群在疾病进展过程中的表达变化。方法选取2018年1月-2019年4月在天津市第二人民医院住院的慢性HBV感染患者共132例,其中慢性乙型肝炎患者47例,乙型肝炎肝硬化患者44例,乙型肝炎肝硬化相关原发性肝癌患者41例。另选取同期健康体检者42例作为对照组。采用流式细胞术检测4组外周血淋巴细胞亚群精准计数,比较4组外周血淋巴细胞亚群的表达水平。正态分布的计量资料,组间方差不齐采用Welch方差分析,两两比较采用GamesHowell检验。非正态分布的计量资料多组间及进一步两两比较采用Kruskal-Wallis H检验。计数资料组间比较采用χ2检验。相关性分析采用Spearman检验。结果与对照组和慢性乙型肝炎组相比,肝硬化组和肝癌组CD3^+、CD4^+T淋巴细胞数量明显减少,差异均有统计学意义(P值均<0.05)。与对照组相比,肝癌组CD8^+T淋巴细胞数量明显减少,差异有统计学意义(P<0.05);与慢性乙型肝炎组相比,肝硬化组和肝癌组CD8^+T淋巴细胞数量明显减少,差异均有统计学意义(P值均<0.05)。与对照组和慢性乙型肝炎组相比,肝硬化组和肝癌组CD19^+B淋巴细胞数量明显减少,差异均有统计学意义(P值均<0.05)。与对照组相比,肝硬化组和肝癌组CD16^+CD56^+NK细胞数量明显减少,差异均有统计学意义(P值均<0.05);与慢性乙型肝炎组比较,肝癌组CD16^+CD56^+NK细胞数量明显减少,差异有统计学意义(P<0.05)。4组疾病进展与外周血CD3^+T淋巴细胞、CD4^+T淋巴细胞、CD8^+T淋巴细胞、CD19^+B淋巴细胞、CD16^+CD56^+NK细胞呈明显负相关(r值分别为-0.414、-0.503、-0.269、-0.435、-0.402,P值均<0.01)。结论随着疾病的进展,慢性HBV感染患者免疫状态发生变化。外周血淋巴细胞亚群精准计数能够反应机体的免疫状态,可作为慢性HBV感染临床病情演变、治疗效果及疾病预后的参考依据。     

肝炎肝硬化患者淋巴细胞亚群与发生感染的关系初探

目的探讨肝炎肝硬化患者发生细菌感染与外周血淋巴细胞亚群各指标的关系。方法选择肝炎肝硬化患者77例,其中发生感染者25例,未发生感染者52例,对2组患者的外周血白细胞数、淋巴细胞亚群绝对数(包括CD_4~+、CD_8~+细胞、NK细胞、B细胞)、CD_4~+/CD_8~+比值进行比较。结果发生感染组CD_4~+ T细胞绝对数(462.38±286.52)较未发生感染组(711.34±501.26)低,P<0.05;感染组CD_8~+ T细胞绝对数(301.46±177.71)也较未发生感染组(482.02±370.48)低,P<0.05。结论肝炎肝硬化患者CD_4~+ T细胞数和CD_8~+ T细胞数低者更容易发生细菌性感染。     

T lymphocyte subsets in autoimmune thyroid diseases and subacute thyroiditis detected with monoclonal antibodies

Peripheral T lymphocyte subsets were analysed with monoclonal antibodies, by highly standardized fluorescence-activated cell sorter analysis instead of manual counting by the indirect immunofluorescence method, in autoimmune thyroid diseases and subacute thyroiditis. Total lymphocyte counts were increased in patients with thyrotoxic Graves' disease and subacute thyroiditis. The percentage of total T (Leu 1) cells was significantly lower in patients with thyrotoxic Graves' disease and Hashimoto's disease with destructive thyrotoxicosis than in normal subjects. No significant changes were observed in the percentages of suppressor-cytotoxic T (Leu 2a) cells or helper-inducer T (Leu 3a) cells or in the Leu 3a-Leu 2a ratio in different groups of patients. There were no correlations between the percentages of E rosette-forming cells and Leu 1 cells and between the percentages of T gamma cells and Leu 2a cells in normal subjects and patients. The peak position of fluorescence intensity of Leu 2a cells showed a significant sex difference even in normal controls. The most important finding was a significant decrease in the peak position of Leu 2a cells in patients with thyrotoxic Graves' disease and with hypothyroid or thyrotoxic Hashimoto's disease. These findings indicate the significant association of qualitative, but not quantitative, abnormality of suppressor-cytotoxic T (Leu 2a) cells with thyroid dysfunction in autoimmune thyroid diseases.