<Emphasis Type="Italic">Mycobacterium tuberculosis</Emphasis> Antigen 85A Induces Th-1 Immune Responses in Systemic Sarcoidosis

Sarcoidosis is a granulomatous disease of unknown etiology, characterized by a Th-1 immunophenotype. Although humoral immune responses by sarcoidosis subjects to mycobacterial proteins have been detected, mycobacterial antigens capable of inducing cellular immune responses in sarcoidosis subjects have not been reported. We used the enzyme-linked immunospot assay to assess for recognition of the Mycobacterium tuberculosis mycolyl transferase, Antigen 85A, by peripheral blood mononuclear cells from 25 sarcoidosis subjects, 22 PPD− (purified protein derivative) healthy volunteers, and 16 PPD+ healthy subjects. Reactivity to Ag85A whole protein was observed in 15 of 25 sarcoidosis subjects compared to 2 of 22 PPD− subjects (p=0.0006, Fisher’s exact test) and to 14 of 16 PPD+ subjects (p=0.084, Fisher’s exact test). Monoclonal antibody against HLA-DR inhibited recognition. In addition to immune recognition of Ag85A whole protein, peptide-mapping studies identified four immunogenic Ag85A peptides, which induced Th-1 immune responses in individual sarcoidosis subjects, suggesting that multiple epitopes from a mycobacterial protein may have a role in sarcoidosis immunopathogenesis.     

Expansion of CD8+ T cells that express low levels of the B cell-specific molecule CD20 in patients with multiple myeloma

An expanded cytotoxic/memory T-cell subpopulation expressing low levels of the B-cell-specific CD20 molecule was found in peripheral blood and bone marrow of patients with multiple myeloma at the time of diagnosis, but returned to normal levels following treatment. CD3+CD20dim cells were also increased in monoclonal gammopathy of unknown significance albeit at lower levels. Lower CD3+CD20dim cell numbers at baseline may be associated with lack of response to treatment and a poor outcome. Because expansion of these T cells may be related to disease status, further studies should investigate their potentially unique function in plasma cell dyscrasias.     

Direct effects on proliferation,antigen expression and melanin synthesis of cultured normal human melanocytes in response to UVB and UVA light

BACKGROUND/PURPOSE: Ultraviolet (UV) radiation; induces a variety of responses in the skin, including tanning and inflammation, and may also act as a carcinogen. As epidermal melanocytes are seen as the major targets of UV light, the present study was conducted to evaluate the direct effects of UVA and UVB irradiation on melanocytes in vitro. METHODS: Normal human epidermal melanocytes (NHM) were exposed on 3 consecutive days to UVA (0.072-7.2 J/cm2) and UVB (7.2-48 mJ/cm2), respectively, and changes of morphology, cell number, melanin synthesis and antigen expression (APAAP technique) were determined 5 days after the first exposure. RESULTS: UVA radiation caused only minimal effects on NHM by slightly inducing expression of the activation marker HMB-45 and decreasing expression of the proliferation marker Ki-67. No changes of morphology, cell number or melanin synthesis were detectable with any of the applied doses. On the other hand, UVB radiation significantly induced dendrite formation and decreased the number of NHM in a dose-dependent manner (74% of the controls at 7.2 mJ/cm2, 64% at 14.4 mJ/cm2 and 28% at 36 mJ/cm2). Significant induction of the activation marker HMB-45 was found in parallel to decreased expression of the differentiation marker K.1.2.58. UVB doses >or=9.6 mJ/cm2 also resulted in significant downregulation of the proliferation marker Ki-67, confirming the data of the cell counts, and melanin content was increased in NHM (20% over the controls, P<0.01) after applying 7.2 mJ/cm2 UVB. CONCLUSION: Our results may suggest that the effect of UVB radiation in skin is due to direct activation of melanocytes, whereas skin tanning caused by UVA is mediated rather in an indirect way.     

In B-cell chronic lymphocytic leukaemia chromosome 17 abnormalities and not trisomy 12 are the single most important cytogenetic abnormalities for the prognosis: A cytogenetic and immunophenotypic study of 480 unselected newly diagnosed patients

Of 560 consecutive, newly diagnosed untreated patients with B CLL submitted for chromosome study, G-banded karyotypes could be obtained in 480 cases (86%). Of these, 345 (72%) had normal karyotypes and 135 (28%) had clonal chromosome abnormalities: trisomy 12 (+12) was found in 40 cases, 20 as +12 alone (+12^single), 20 as +12 with additional abnormalities (+12^complex). Other frequent findings included abnormalities of 14q, chromosome 17, 13q and 6q. The immunophenotype was typical for CLL in 358 patients (CD5⁺, Slg^weak, mainly FMC7⁻) and atypical for CLL in 122 patients (25%) (CD5⁻, or Slg^strong or FMC7⁺). Chromosome abnormalities were found significantly more often in patients with atypical (48%) than in patients with typical CLL phenotype (22%) (P < 0.00005). Also +12^complex, 14q +, del6q, and abnormalities of chromosome 17 were significantly more frequent in patients with atypical CLL phenotype, whereas +12^single was found equally often in patients with typical and atypical CLL phenotype. The cytomorphology of most of the +12 patients was that of classical CLL irrespective of phenotype. In univariate survival analysis the following cytogenetic findings were significantly correlated to a poor prognosis: chromosome 17 abnormalities, 14q +, an abnormal karyotype, +12^complex, more than one cytogenetic event, and the relative number of abnormal mitoses. In multivariate survival analysis chromosome 17 abnormalities were the only cytogenetic findings with independent prognostic value irrespective of immunophenotype.We conclude that in patients with typical CLL immunopenotype, chromosome abnormalities are somewhat less frequent at the time of diagnosis than hitherto believed. +12^single is compatible with classical CLL, and has no prognostic influence whereas chromosome 17 abnormalities signify a poor prognosis. In patients with an atypical CLL immunophenotype, chromosome abnormalities including +12^complex, 14q +, del 6q and chromosome 17 are found in about 50% of the patients, and in particular chromosome 17 abnormalities suggest a poor prognosis.     

非何杰金淋巴瘤免疫表型和基因型分析

采用单克隆抗体免疫酶法和体外基因扩增聚合酶链反应技术研究25例非何杰金淋巴瘤免疫表型及其中8例免疫球蛋白和T细胞受体基因重排的基因型。14例表达B系细胞分化抗原者中,5例起源于前B细胞,9例起源于晚期成熟B细牌。表达T系细胞分化抗原者9例,起源于幼稚或成熟胸腺细胞者各4例,普通胸腺细胞者1例。另有2例同时表达了T、B系细胞分化抗原。8例基因分析者中。4例表达B系和3例表达T系细胞分化抗原者分别检测到IgH和TCR_γ基因克隆性重排。1例表达T、B系细胞分化抗原者出现IgH基因重排和TCR_δ基因缺失。讨论了非何杰金淋巴瘤免疫表型和基因重排分析的临床应用价值。     

Primary Pleomorphic T-cell Lymphoma of the Spleen

We report a case of primary splenic T-cell lymphoma that posed difficult problems in differential diagnosis with erythrophagocytic T-gamma lymphoma and inflammatory pseudotumor of the spleen. The need for immunophenotypic and molecular studies for establishing the correct diagnosis and the importance of early detection and treatment, is emphasized in the light of the relatively good prognosis of splenic lymphoma, diagnosed in the early stages of disease.     

T cells in myeloma

The current trend to develop immunotherapy strategies for patients with myeloma and other B cell malignancies has stimulated considerable interest in the functional state of the T cell population in these patients. Expanded clones of T cells exist in many patients with myeloma and their presence is associated with an improved survival. However, isolating T cells with tumour specificity has proven to be a difficult task and clinical immunization trials have so far failed to achieve a significant response. There is now evidence that tumour specific T cells are either tolerized or deleted following antigen presentation and that idiotype-derived, immunodominant tumour peptides may not exist in all patients. In order to develop more effective immunotherapy strategies for patients with myeloma, further studies are urgently required to identify the most appropriate tumour antigen, the nature of the interactions which take place during antigen presentation, and how to promote the cytotoxicity of autologous T cells.     

急性粒细胞白血病患儿免疫表型及其临床意义

目的探讨儿童急性粒细胞白血病（AML）免疫分型及其临床意义。方法总结81例儿童AML的免疫表型与FAB分类、1个月骨髓缓解（CR）率及3年无病生存（EFS）率的关系。结果AML儿童1个月CR率为71.6%,3年EFS率为50.8%。HLA-DR缺失,CD34缺失主要见于急性早幼粒细胞白血病（M3）型,阴性患儿CR、EFS率明显高于阳性患儿。CD13阳性患儿的CR明显高于缺失患儿。CD33缺失在M2型中多见,特别是ETO阳性患儿。除外M3病例后分析,CD33缺失患儿的CR率明显高于阳性患者。淋系抗原表达率占34.6%,其中CD7阳性者CR率、EFS率均低于对照组,但无统计学差异。CD56与FAB分型中M2型有显著相关性,其CR率、EFS率均低于对照组。结论HLA-DR、CD34缺失主要见于M3型,是预后良好的指标。CD33缺失多见于M2型中ETO阳性患儿,预后好。淋系抗原、CD56表达多见于M2型,可能是预后差的指标。     

急性混合性白血病5例临床、细胞形态学及免疫表型的观察

目的进一步了解急性混合性白血病（ＡＭＬＬ）临床细胞、形态学及免疫学等特点。方法在对１２９例急性白血病（ＡＬ）全面检查及分析的基础上,对其中５例ＡＭＬＬ的临床细胞形态学、细胞化学及免疫表型等进行分析。结果５例ＡＭＬＬ在细胞形态学、细胞化学及免疫表型等方面均表现淋和髓二系特征。免疫表型除均同时表达淋和髓相关抗原外,还均表达ＨＬＡ－ＤＲ抗原。其中１例尚同时表达ＣＤ７和ＣＤ３４。３例在住院治疗观察中,发现对较强的针对淋系和髓系白血病的联合化疗反应差。结论分析ＡＭＬＬ临床、细胞形态学及免疫学等特点,对于ＡＭＬＬ的诊断和指导治疗均有重要意义