Comparison of allergenicity and immunogenicity of an intact allergen vaccine and commercially available allergoid products for birch pollen immunotherapy

BACKGROUND: Specific immunotherapy with intact allergen vaccine is a well-documented treatment for allergic diseases. Different vaccine formulations are currently commercially available, the active ingredient either being intact allergens or chemically modified allergoids. The rationale behind allergoids is to decrease allergenicity while maintaining immunogenicity. However, data from the German health authorities based on reporting of adverse events over a 10-year period did not indicate increased safety of allergoids over intact allergens. OBJECTIVE: The objective of this study was to investigate the effect of chemical modification on allergenicity and immunogenicity comparing four commercial allergoid products for birch pollen immunotherapy with an intact allergen vaccine. METHODS: Solid-phase IgE inhibition and histamine release assays were selected as model systems for allergenicity, and a combination of human T cell proliferation and IgG titres following mouse immunizations were used to address the immunogenicity of the intact allergen vaccine and the four allergoids. In all assays, the products were normalized with respect to the manufacturer's recommended maintenance dose. RESULTS: IgE inhibition experiments showed a change in epitope composition comparing intact allergen vaccine with allergoid. One allergoid product induced enhanced histamine release compared to the intact allergens, while the other three allergoids showed reduced release. Standard T cell stimulation assays using lines from allergic patients showed a reduced response for all allergoids compared with the intact allergen vaccine regardless of the cell type used for antigen presentation. All allergoids showed reduced capacity to induce allergen-specific IgG responses in mice. CONCLUSION: While some allergoids were associated with reduced allergenicity, a clear reduction in immunogenicity was observed for all allergoid products compared with the intact allergen vaccine, and the commercial allergoids tested therefore do not fulfil the allergoid concept.     

Lymphoma phenotyping in formalin-fixed and paraffin wax-embedded tissues. I. Range of antibodies and staining patterns

Recently, monoclonal antibodies capable of phenotyping malignant lymphomas in routinely fixed and processed tissue have become available. Some of these reagents identify lineage-restricted variants of the leucocyte common molecule, whereas others identify unique fixation-resistant epitopes on lymphoid cells, some of which are shared by non-lymphoid tissues. A new generation of antibodies recognizing 'classical' leucocyte antigens such as CD3 are also emerging. Refinements in antigen detection systems, especially for immunoglobulin recognition, combined with these new reagents promise to improve the accuracy of lymphoma diagnosis in routine histopathology. These new antibodies are reviewed, and their limitations, cross reactivities and profiles of staining in lymphoreticular disease are discussed. A strategy for their optimal use is proposed.     

88例恶性淋巴瘤预后相关资料分析

目的：了解恶性淋巴瘤（ML）发病、病理及免疫分型特点，探讨基因分型在诊断中的作用。方法：通过标准链菌素生物素－过氧化物酶标记物法（SABC法）对病理标本进行免疫分型，PCR检测病理及骨髓标本IgH（FR2A，3A）和TCR（β，γ）基因重排，同时对临床及病理资料进行多因素分析。结果：（1）ML非霍奇金淋巴瘤（NHL）较霍奇金淋巴瘤（HL）发病率高，发病率随年龄增长而递增，60岁以上发病者占38．6％；其平均生存时间明显低于60岁以下者。（2）B－NHL发病率为68．6％，T－NHL为28．6％；B－NHL的3年生存率高于T－NHL。（3）低度恶性NHL占42％，中、高度恶性占58％；低度恶性组平均生存时间较中、高度恶性组长，但统计学上差异无显著性。生存期分析显示I－Ⅱ期NHL预后明显优于Ⅲ－Ⅳ期。（4）PCR检测病理及骨髓标本的IgH和TCR重排，B－NHL FR2A的阳性率分别为66.7%及56．2％；FR3A阳性率分别为90．4％及81．2％；T－NHL中TCRβ、γ阳性率分别为91．7％及75．0％；病理标本的阳性率略高于骨髓，T、B分型与免疫分型相符。结论：年龄，T、B分型和临床分期是影响NHL预后的重要因素；分子生物学检测作为辅助手段可以肯定免疫分型结果并补充其不足，骨髓及外周血检测除协助分型外可用于肿瘤微小残留病的监测。     

Paraneoplastic movement disorder in a patient with non-Hodgkin's lymphoma and CRMP-5 autoantibody.

The paraneoplastic autoantibody, collapsin response-mediator protein (CRMP)-5 immunoglobulin G (IgG), is specific for neuronal cytoplasmic CRMP-5, and is usually associated with small-cell lung carcinoma or thymoma. We report on details of a movement disorder that followed anti-B-cell therapy in a patient with lymphoma, and was accompanied by CRMP-5 IgG.     

Revisiting the prognostic role of gallium scintigraphy in low-grade Non-Hodgkin’s lymphoma

The purpose of this study was threefold: to evaluate the role of gallium-67 scintigraphy in the staging of low-grade non-Hodgkin’s lymphomas (LGNHL), to assess the relationship between the expression of CD71 on the surface of the neoplastic cells and the ⁶⁷Ga uptake by the tumour, and to establish the contribution of ⁶⁷Ga scan in defining the prognosis of LGNHL. Forty-eight patients with untreated LGNHL diagnosed in a single institution over a decade were reviewed. The end point of the study was survival of the patients according to the scintigraphic ⁶⁷Ga score at diagnosis. In addition to ⁶⁷Ga scan, other prognostic variables were studied, relating to the neoplastic burden, the biology of the tumour and the host. Univariate and multivariate analyses were used. ⁶⁷Ga scan identified only 116/286 (41%) nodes involved by lymphoma that were detected by clinical examination or computed tomography scan. A scintigraphic scoring system with an arbitrary cut-off value of 3 (high scan score) was able to predict patients with a dismal prognosis: with a mean follow-up of 47 months (range: 1–146 months) the median survival time was 28 months in patients with a high scan score and 74 months in patients with a low scan score (P=0.002). CD71 values were 27.4%±14.9% (mean ±SD) in the former and 8.9%±7.2% in the latter (P=0.0001). Only performance status and extranodal sites were significant variables for prognosis in multivariate analysis. It is concluded that ⁶⁷Ga scan is inaccurate in staging but might be very important in defining the prognosis in LGNHL, in association with other prognostic variables. Received 1 May and in revised form 6 August 1997     

A new monoclonal antibody which binds to the cytoplasm of large cell lymphomas.

We reported a new monoclonal antibody, designated FUB-1, reacting with normal and neoplastic large lymphoid cells. FUB-1 was produced using a Burkitt's lymphoma cell line (HBL-5) as an immunogen. Its immunoglobulin subtype was IgM. The determinant was not on the surface but in the cytoplasm. Western blotting analysis revealed that the molecular weight of the antigen was 52,000 dalton. In the normal lymphoid tissue, FUB-1 reacted with large lymphoid cells, but not with small or medium-sized lymphoid cells or plasma cells. In addition, the FUB-1 antigen was not found in resting cells in the peripheral blood (PB), but it was induced on mononuclear cells of PB by addition of PWM or PMA. In the B-cell lymphomas tested, FUB-1 reacted with small cleaved cell lymphomas (3/12), large cell lymphomas (7/10), Burkitt's lymphomas (4/4) and immunoblastic lymphomas (2/2), but not with small cell lymphomas (0/3) or intermediate lymphocytic lymphomas (0/8). These findings indicate that the FUB-1 antigen appears to be expressed on normal lymphoid cells during blastoid transformation and on neoplastic large lymphoid cells. FUB-1 also reacted with normal glandular epithelium and various adenocarcinomas. FUB-1 may be useful to investigate the mechanism of in vitro blastoid transformation or activation of lymphoid cells.     

T Cell Receptor Vβ Repertoires of Angioimmunoblastic Lymphadenopathy-like T Cell Lymphoma

To elucidate the pathogenesis of angioimmunoblastic lymphadenopathy-like T cell lymphoma (AILD-T) we investigated the T cell receptor Vβ gene repertoires of four AILD-Ts and compared them with those of other histological types of lymphomas and three cases with reactive disorders. All lymphoma patients had rearrangement bands detected by Southern blot analysis. Only 1 of the 4 cases of AILD-T showed a single predominant usage of Vβ 20 gene by PCR with 20 different Vβ specific primers and the others had repertoires somewhat restricted but similar to reactive lesions. Subsequent sequencing of this PCR product revealed that only 2 of 7 clones were identical. These results suggest the monoclonal malignant cells in AILD-T are scant and that the infiltrating T cells show a reactive pattern. In the only AILD-T case with a single dominant Vβ usage, the relationships of this repertoire and lymphoma cells seems to be of some consequence.     

Lateral position prevents respiratory occlusion during surgical procedure under general anesthesia in the patient of huge anterior mediastinal lymphoblastic lymphoma

Lymphoblastic lymphoma, an aggressive mediastinal mass, is recognized as serious threat to the patient in developing cardiac tamponade or airway obstruction. Surgical procedure is often required to relieve clinical emergency and to establish prompt pathological diagnosis. However, in such a patient, acute respiratory occlusion in the spine position can be a life-threatening complication during general anesthesia. We describe a 17-year-old man whose cardiac tamponade was treated by pericardial-pleural window through a left anterior thoracotomy in the lateral position. The patient recovered from hemodynamic compromise without showing respiratory occlusion during general anesthesia and remained in the lateral position until extubation. Pathological diagnosis was precursor T-lymphoblastic lymphoma. There were no complications attributable to the operative procedure. Further chemotherapy reduced the mediastinal mass in size after two weeks when the patient developed sepsis and died. Lateral position prevents respiratory occlusion during surgical procedure under general anesthesia in the patient of huge anterior mediastinal tumor with airway obstruction.     

34例淋巴瘤骨髓浸润患者治疗与预后分析

目的 探讨淋巴瘤骨髓浸润患者的治疗与预后。方法 34例淋巴瘤骨髓浸润患者分为单纯化疗组、化疗+放疗组、大剂量化疗+自体干细胞移植组进行治疗,长期随访,分析其预后状况。结果 全组中位生存期为20个月;1年和3年生存率分别为76.47％和26.47％,最初疗效为完全缓解和部分缓解患者的1年和3年生存率均大于未缓解患者(P<0.05);大剂量化疗+自体干细胞移植组的3年生存率大于单纯化疗组和化疗+放疗组(P<0.05)。结论 淋巴瘤骨髓浸润患者的生存率与最初疗效有关;大剂量化疗+自体干细胞移植能提高其生存率,改善预后。     

原发性胃肠道淋巴瘤的诊断与治疗

目的探讨原发性胃肠道淋巴瘤的诊治经验。方法回顾性分析12例原发性胃肠道淋巴瘤,均行剖腹探查,其中行根治性切除7例,姑息性手术3例,肿块活检术2例。结果胃淋巴瘤5例,肠淋巴瘤7例。病理分类:弥漫性非何杰金氏淋巴瘤9例,粘膜相关性淋巴瘤2例,高度恶性淋巴瘤1例。Ann Arbor临床分期:ⅡE期3例,ⅢE期7例,ⅣE期2例。平均随访18(6~72)月,6例存活,死亡6例。结论内镜和消化道造影是淋巴瘤主要诊断手段,手术切除为主的综合治疗为最佳治疗方案。