Hodak E, Lapidoth M, Kohn K, David D, Brautbar B, Kfir K, Narinski N, Safirman S, Maron M, Klein K
Department of Dermatology, Rabin Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Petah Tiqva, Israel.
Br J Dermatol. 2001 Dec;145(6):974-80. doi: 10.1046/j.1365-2133.2001.04496.x.
An immunogenetic mechanism has been suggested to play a role in the pathogenesis of mycosis fungoides (MF). While results of studies on HLA class I associations haveproved inconsistent, two previous studies showed that certain HLA class II alleles were significantly increased among North American caucasian patients with MF: HLA-DRB111 and DQB103.
To investigate the possible HLA class I and class II associations with MF among Jewish patients.
The patient group comprised 68 Jewish patients with MF: 38 Ashkenazi and 30 non-Ashkenazi. The control group comprised 252 healthy Jewish volunteers: 132 Ashkenazi and 120 non-Ashkenazi. Tissue typing for HLA class I (A and B) was performed using the National Institutes of Health microlymphocytotoxicity technique. DNA-based low-medium resolution analysis for DRB1* and DQB1* alleles was performed using polymerase chain reaction (PCR) amplification with sequence-specific primers. For those alleles found to have significantly increased frequency, high-resolution analysis was done by means of PCR sequence-specific oligotyping.
The allele frequency of HLA-DRB111 was found to be significantly increased but only among Ashkenazi patients with MF (30% vs. 19% in the controls; P = 0.034). High-resolution analysis for DRB111, not previously performed, suggested that its greater frequency is due to the increased number of Ashkenazi MF patients with the DRB11104 allele (P corrected = 0.036). Analysed together, DQB103 alleles (DQB10301-0304) had a significantly greater frequency in MF as a group as compared with controls (47% vs. 33%, P = 0.003). DQB10301 was demonstrated to be the specific allele associated with MF in Jewish patients (allele frequency of 36% vs. 23% in controls; P corrected = 0.0068), which was not the case for North American caucasian patients with MF. No greater frequencies of any of the HLA class I A or B antigens were found.
Our findings further demonstrate the 'universality' of MF HLA class II susceptibility alleles, i.e. HLA-DRB111 and HLA-DQB103, suggesting that HLA polymorphism is likely to be important in the pathogenesis of MF in Jewish patients, as it is in North American caucasian patients. Not previously reported is our finding that HLA-DRB1*1104 is the specific allele more prevalent among patients with MF. Our study also underscores some differences in HLA profiles between non-Jewish and Jewish patients with MF and between Ashkenazi and non-Ashkenazi Jewish patients, indicating the possibility of diverse HLA disease associations in populations with different genetic backgrounds. Our study provides further evidence for the lack of association between HLA class I and MF.
有免疫遗传机制被认为在蕈样肉芽肿（MF）的发病机制中起作用。虽然关于HLA I类相关性的研究结果并不一致，但此前两项研究表明，在北美白种MF患者中，某些HLA II类等位基因显著增加：HLA - DRB111和DQB103。
研究犹太患者中MF与HLA I类和II类的可能相关性。
患者组包括68例犹太MF患者：38例阿什肯纳兹人及30例非阿什肯纳兹人。对照组包括252名健康犹太志愿者：132例阿什肯纳兹人及120例非阿什肯纳兹人。采用美国国立卫生研究院微淋巴细胞毒性技术进行HLA I类（A和B）组织分型。使用序列特异性引物的聚合酶链反应（PCR）扩增对DRB1和DQB1等位基因进行基于DNA的低中分辨率分析。对于那些频率显著增加的等位基因，通过PCR序列特异性寡核苷酸分型进行高分辨率分析。
发现HLA - DRB111的等位基因频率显著增加，但仅在阿什肯纳兹MF患者中（30%对对照组的19%；P = 0.034）。此前未进行过的DRB111高分辨率分析表明，其频率较高是由于携带DRB11104等位基因的阿什肯纳兹MF患者数量增加（校正P = 0.036）。综合分析，DQB103等位基因（DQB10301 - 0304）在MF患者组中的频率显著高于对照组（47%对33%，P = 0.003）。DQB10301被证明是与犹太MF患者相关的特异性等位基因（等位基因频率为36%对对照组的23%；校正P = 0.0068），而北美白种MF患者并非如此。未发现HLA I类A或B抗原的频率有增加。
我们的研究结果进一步证明了MF HLA II类易感等位基因即HLA - DRB111和HLA - DQB103的“普遍性”，表明HLA多态性可能在犹太患者MF的发病机制中起重要作用，如同在北美白种患者中一样。我们发现HLA - DRB1*1104是在MF患者中更普遍的特异性等位基因，这一发现此前未见报道。我们的研究还强调了非犹太和犹太MF患者之间以及阿什肯纳兹和非阿什肯纳兹犹太患者之间HLA谱的一些差异，表明在不同遗传背景人群中存在不同的HLA疾病关联可能性。我们的研究为HLA I类与MF缺乏关联提供了进一步证据。
