自身免疫与淋巴瘤

 自身免疫和淋巴瘤之间有双重相关性,即自身免疫性疾病患者淋巴瘤发生率增高,同时淋巴瘤患者易合并自身免疫现象。现对自身免疫性疾病患者发生淋巴瘤和淋巴瘤患者合并自身免疫现象的流行病学情况、临床特点以及内在机制等方面的新进展进行综述。     

Siglec家族成员在免疫调控与免疫病理中作用的研究进展

唾液酸结合性免疫球蛋白样凝集素（sialic acid-binding Ig-like lectins,Siglecs）是一类免疫球蛋白超家族（immunoglobulin superfamily, IgSF）成员,可通过识别含有唾液酸的糖链结构,介导细胞与细胞或病原体间的相互作用,在固有免疫和适应性免疫中发挥重要的调控作用。近年来研究表明,Siglec家族成员参与免疫细胞活化、增殖以及凋亡的调控;同时,Siglec家族成员也参与免疫耐受的调控,并在自身免疫病、炎症反应以及肿瘤发生中发挥重要的免疫调控作用;因此,越来越多的靶向Siglecs抗体或糖基化配体的治疗药物被相继研发并用于淋巴瘤、白血病和自身免疫疾病等多种Siglecs相关疾病的治疗。现就Siglecs参与免疫调控及其在抗自身免疫病和抗肿瘤发生中的研究进展作一综述。     

EB病毒感染的多样性及其意义

EB病毒(Epstein-Barr virus,EBV)是最早被确定的人类肿瘤病毒,在人群中广泛传播,感染呈多样性.EBV与伯基特淋巴瘤、霍奇金淋巴瘤等多种淋巴瘤以及鼻咽癌、胃癌等多种实体肿瘤相关,还能引起移植后淋巴增生性疾病和自身免疫病等多种疾患.EBV以隐性感染的方式终身潜伏,在少数免疫力低下者体内通过多种途径在多...     

肿瘤与自身免疫

肿瘤和自身免疫性疾病密切相关。肿瘤患者有很多自身免疫现象,而自身免疫性疾病患者中肿瘤患病率也高于正常人群。本文综述目前在恶性肿瘤中最常伴发的自身免疫性疾病以及出现在患者体内的自身抗体,简述自身免疫性疾病恶性转化的可能机制。     

伴自身免疫性疾病的骨髓增生异常综合征的临床特点

目的 探讨骨髓增生异常综合征(MDS)与自身免疫性疾病的相关性及其临床意义。方法 回顾分析7例伴自身免疫性疾病的MDS的临床及实验特点。结果 7例伴发的自身免疫性疾病中,白塞病2例,类风湿性关节炎、Crohn’s病、抗D抗体阳性的输血性溶血性贫血、Sweet's综合征及坏疽性脓皮病各1例。3例自身免疫性疾病发生于MDS之前,1例与MDS同时发生,3例发生于MDS之后。7例患者经糖皮质激素及免疫抑制剂治疗后,自身免疫性疾病均得以明显缓解,但MDS预后仍较差,其中2例在半年内转变为急性髓细胞白血病,化疗后均未缓解而死亡,3例死于RA期,其他正在治疗中。结论 部分MDS与自身免疫性疾病有密切联系,伴自身免疫性疾病是MDS预后不良的因素。     

Castleman病与淋巴瘤相关性研究进展

Castleman病是一种发病机制未明的淋巴组织增生性疾病。近年来有研究发现Castleman病可与淋巴瘤同时或先后诊断,部分淋巴瘤患者的淋巴结也可出现Castleman病样特征的改变,本文旨在对Castleman病与淋巴瘤的相关性及发病机制进行综述。     

补体系统在淋巴瘤中的作用研究进展

补体系统是一个具有精细调控机制的蛋白质反应系统，是机体固有免疫和适应性免疫的重要组成部分。补体成分异常、过度活化等功能障碍与淋巴瘤的发生、发展和免疫逃逸密切相关。此外对于临床治疗，尤其免疫治疗具有一定相关性。现就补体系统在淋巴瘤发生及治疗中的作用进行综述。     

淋巴瘤样丘疹病C型一例报道及文献复习

背景与目的:原发皮肤CD30阳性淋巴增生性疾病谱中,关于淋巴瘤样丘疹病和原发皮肤间变性大细胞淋巴瘤的文献报道较常见,而其中的界限性病变--淋巴瘤样丘疹病c型的报道则较少见,故本文介绍与探讨1例淋巴瘤样丘疹病C型的临床表现、形态学特点以及免疫表型特征,旨在提高对此病的认识.方法:对华山医院诊断的1例皮肤淋巴瘤样丘疹病 C型患者的临床表现、组织病理学形态及免疫组织化学结果进行研究,并结合文献复习.结果:患者全身反复发作的散发性红疹伴瘙痒,可自行缓慢消退.患者全身皮肤可见多发性丘疹样病变,病变严重处出现脓疱并破溃结黑痂.组织学上,表皮溃疡并脱失,真皮层见中等偏大淋巴细胞浸润.细胞免疫表型CD30、CD3、TIA-1等呈阳性表达,ALK、CD20阴性.结论:皮肤淋巴瘤样丘疹病c型较少见,需与原发皮肤间变性大细胞淋巴瘤及系统性间变性大细胞淋巴瘤累及皮肤病变等鉴别,其诊断需结合临床表现、病理学形态及免疫表型等以明确其性质.     

EBV相关肿瘤的发生机制及其免疫靶向治疗的研究进展

作为WHO宣布的Ⅰ类致癌物EBV,其与移植后淋巴组织增生性疾病、霍奇金淋巴瘤（HL）、伯基特淋巴瘤、鼻咽癌、 EBV相关性胃癌等恶性肿瘤的发生相关,且具有作为预后预测指标及治疗靶点的潜能。目前,EBV免疫靶向治疗研究取得了众 多进展,基于EBV疫苗的主动免疫疗法和直接输注EBV-CTL的过继免疫疗法均可激活EBV特异性免疫应答并改善患者生存, PD-1/PD-L1抑制剂和IDO抑制剂联合可通过增强免疫应答、减少免疫逃逸而在EBV相关肿瘤中发挥抗肿瘤作用。此外,某些去 甲基化及去乙酰化药物可靶向作用于EBV阳性肿瘤细胞,诱导EBV病毒基因裂解。未来有望通过靶向治疗及免疫治疗的联合 应用为EBV相关肿瘤患者赢得更好的预后。     

结缔组织病合并恶性肿瘤的临床分析

结缔组织病(connective tissue disease,CTD)又称胶原性疾病,是一类非器官特异性自身免疫疾病,以血管和结缔组织慢性非化脓性炎症、增生和变性的病理改变为基础,病变累及多个系统,临床个体差异甚大.关于CTD尤其皮肌炎与肿瘤发生有密切相关性的报道并不少见,并且以成人多见,且各个年龄段都有发生肿瘤的危险.     

Autoimmune hemolytic anemia and autoimmune thrombocytopenia at diagnosis and during follow-up of Hodgkin lymphoma

Autoimmune hemolytic anemia and thrombocytopenia (AIHA/AITP) frequently complicate the course of non-Hodgkin lymphomas, especially low-grade, but they are very rarely observed in Hodgkin lymphoma (HL). Consequently the frequency and the profile of patients with HL-associated AIHA/AITP have not been well defined. Among 1029 patients with HL diagnosed between 1990 and 2010, two cases of AIHA (0.19%) and three of AITP (0.29%) were identified at the presentation of disease. These patients were significantly older, and more frequently had features of advanced disease and non-nodular sclerosing histology, compared to the majority of patients, who did not have autoimmune cytopenias at diagnosis. ABVD combination chemotherapy (doxorubicin, bleomycin, vinblastine, dacarbazine) provided effective control of HL and the autoimmune condition as well. During approximately 6600 person-years of follow-up for the remaining 1024 patients, seven (0.7%) patients developed autoimmune cytopenias (three AITP, three AIHA, one autoimmune pancytopenia) for a 10- and 15-year actuarial incidence of 0.95% and 1.40%, respectively. Their features did not differ compared to the general population of adult HL. In this large series of consecutive, unselected patients, those who presented with autoimmune cytopenias had a particular demographic and disease-related profile. In contrast, patients developing autoimmune cytopenias during follow-up did not appear to differ significantly from those who did not.     

Susceptibility to lymphoid neoplasia in immunodeficient strains of nonobese diabetic mice

Transformed lymphocytes exhibit aberrant growth potential resulting from enhanced proliferation and resistance to apoptotic stimuli. These mechanisms also influence the development of autoimmune disease, where dysregulated lymphocyte homeostasis has been implicated in expansion of autoreactive T cells. In the nonobese diabetic (NOD) mouse, a murine model of autoimmune type 1 diabetes and Sj?gren's syndrome, T cells are apoptosis resistant compared with other mouse strains, a feature thought to potentiate their autoimmune function. NOD mice congenic for the severe combined immunodeficiency scid mutation (NOD.scid) have an incidence of pro-T-cell lymphoma far in excess of scid mutants on other genetic backgrounds. This mutation arrests lymphocyte development secondary to a generalized defect in double-strand DNA break repair that compromises V(D)J recombination. To distinguish between the contributions of immunodeficiency and defective double-strand DNA break repair to lymphoma susceptibility on the NOD background, we examined the incidence, phenotype, and molecular mechanisms of lymphoma development in two immunodeficient NOD strains with normal DNA repair function. We report that NOD mice deficient in mature B cells (NOD. micro MT) or mature T and B cells (NOD.RAG-2(-/-)) display a high incidence of lymphoma of both T- and B-cell origin compared with these mutations on other genetic backgrounds. Strikingly, the lymphoma incidence in both strains was greater in females, mirroring the greater incidence of autoimmune type 1 diabetes in NOD females than in males. The high incidence of autoimmune diabetes and lymphoma in immunodeficiency NOD mice suggests the presence of genetic modifiers that affect lymphocyte homeostasis.     

Autoantibodies in the sera of patients with lymphoma.

Sera of 84 patients with Hodgkin's disease (HD) and 55 patients with non-Hodgkin's lymphoma (NHL) were examined for the presence of autoantibodies to ssDNA, dsDNA, Poly (I), Poly (G), cardiolipin, histones, RNP. Sm, Ro (SS/A), La (SS/B) and the common anti-DNA idiotype (16/6) using an enzyme-linked immunosorbent assay (ELISA). Anti-ssDNA antibodies were detected in the sera of 20 patients with lymphoma (23.8%), more among those with NHL than HD (16 vs. 4 patients p < 0.01). Anti-RNP and anti-Sm antibodies were found in 16 (21.7%) and 14 lymphoma patients (20%) respectively, significantly more than in the controls (p < 0.05) in both antibodies). These findings remained valid following subgrouping of the patients into those with HD and NHL. With all the other autoantibodies examined no significant difference could be observed in the incidence between lymphoma patients and controls. These results differ from our previous survey carried out on sera of patients with solid tumors in whom no increased frequency of any of the autoantibodies could be determined. In view of the evidence suggesting an increased risk of lymphoma in a number of autoimmune diseases our results extend this relationship to an increased incidence of autoantibodies among patients with lymphoma.     

Cancer among children of parents with autoimmune diseases

Many different aetiologies for childhood cancer have been suggested, but few are well established. One is that parental autoimmune disease is linked with susceptibility for haematopoietic malignancies in their offspring during childhood. The present study is the first to investigate this hypothesis using a follow-up design. A cohort of 53,811 children of more than 36,000 patients diagnosed with a systemic, organ-specific or suspected autoimmune disease were followed up for cancer incidence in the Danish Cancer Registry during 1968-1993. The parents were identified through the National Registry of Patients, while their children were traced in the Central Population Register. Cancer incidence among the offspring was compared with that in the corresponding childhood population of Denmark. In total, 115 cancers were observed among children aged 0-19 years, yielding a non-significant standardized incidence ratio of 1.07. Lymphomas contributed 21 cases to the overall number of tumours, 60% more than expected (95% confidence interval (CI) 1.0-2.4); leukaemia contributed 37 cases representing an excess of 30% (95% CI 0.9-1.8). Our results give some support to the hypothesis that parental autoimmune disease is associated with childhood lymphoma and leukaemia.     

Autoantibodies in gastric MALT-type lymphoma.

The significance of underlying autoimmune diseases in gastricMALT-type lymphoma is a matter of debate. Recently, Raderer et al. [1] reported an impaired response of gastric low-gradeMALT-type lymphoma to Helicobacter pylori eradication in a smallcollective of patients suffering from autoimmune diseases. Stimulated by this study we     

Autoimmunity and lymphomagenesis

For more than 50 years, links between autoimmunity and lymphomas have been described based on human and animal studies. Over the last 3 decades, many studies have addressed specific hypotheses about these associations using population level data. This has been accomplished by assessing previous autoimmune history in case–control studies of patients with lymphoma (mainly non‐Hodgkin lymphoma) and myeloma, and by following cohorts of patients with various autoimmune diseases for subsequent development of lymphoma and multiple myeloma. In this article, we review our recently published series of association studies based on data from Scandinavia and from US Veterans and other relevant findings. We also discuss what these associations have revealed about the mechanisms and pathways underlying both autoimmunity and lymphoma. Finally, we discuss the future directions involving a combination of population and molecular studies that are needed to better define underlying biological mechanisms. Published 2008 Wiley‐Liss, Inc.     

A malignancy work-up in patients with cancer-associated (paraneoplastic) autoimmune diseases: pemphigus and myasthenic syndromes as cases in point (review)

Although some autoimmune diseases are known to be associated with a higher incidence of cancers, they are not usually considered as paraneoplastic diseases, but rather as autoimmune diseases that may be neoplasia-associated, since currently it is not known whether the tumor leads to their development, or alternatively another underlying condition turns the patients prone to both cancer and autoimmunity. We review the association of cancer with pemphigus, paraneoplastic pemphigus, myasthenia gravis and Eaton-Lambert syndrome, and discuss the importance of looking for an occult malignancy in a patient with a newly-diagnosed autoimmune disease that is known to be associated with cancer.     

自身免疫性疾病相关性非霍奇金淋巴瘤的研究进展

近年来关于自身免疫性疾病（ADs）相关性非霍奇金淋巴瘤（NHL）的研究和报道越来越多,目前已经发现多种ADs会增加NHL的发病风险,然而不同类型的ADs发生NHL的危险性不尽相同,发生NHL的病理类型也有一定的倾向性。导致这一现象的生物学机制值得进一步探讨。本文将对目前研究发现与增加NHL发生风险有关的ADs以及ADs相关性NHL的临床特点、生物学机制和治疗等方面作一综述。     

Risk of cancer of unknown primary after hospitalization for autoimmune diseases

Cancer of unknown primary (CUP) is a heterogeneous syndrome diagnosed at metastatic sites. The etiology is unknown but immune dysfunction may be a contributing factor. Patients with autoimmune diseases were identified from the Swedish Hospital Discharge Register and linked to the Swedish Cancer Registry. Standardized incidence ratios (SIRs) were calculated for subsequent CUP and compared with subjects without autoimmune diseases. A total of 789,681 patients were hospitalized for any of 32 autoimmune diseases during years 1964–2012; 2,658 developed subsequent CUP, giving an overall SIR of 1.27. A total of 16 autoimmune diseases were associated with an increased risk for CUP; polymyositis/dermatomyositis showed the highest SIR of 3.51, followed by primary biliary cirrhosis (1.81) and Addison's disease (1.77). CUP risk is known to be reduced in long‐time users of pain‐relieving nonsteroidal anti‐inflammatory drugs (NSAIDs), such as aspirin. For patients with ankylosing spondylitis and with some other autoimmune diseases, with assumed chronic medication by NSAIDSs, CUP risks decreased in long‐term follow‐up. The overall risk of CUP was increased among patients diagnosed with autoimmune diseases, which call for clinical attention and suggest a possible role of immune dysfunction in CUP. The associations with many autoimmune diseases were weak which may imply that autoimmunity may not synergize with CUP‐related immune dysfunction. However, long‐term NSAID medication probably helped to curtail risks in some autoimmune diseases and CUP risks were generally higher in autoimmune diseases for which NSAIDs are not used and for these CUP appears to be a serious side effect.