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目的本周蛋白(BJP)在多发性骨髓瘤(MM)肾损害中起主要作用,本研究试图探讨BJP基因可变区特点与肾小管功能损害的关系。方法将初诊时肾小管功能明显损害且肾组织穿刺活检提示管型肾病的患者分为损害组,确诊后长期BJP阳性而肾小管功能正常的MM患者为无损害组,根据BJP不同,分为BJPκ组与BJPλ组。常规抽取所有患者骨髓提取单个核细胞,提取总RNA,逆转录成cDNA,PCR扩克隆BJP可变区基因、测序,通过Internet网与GenBank已收录的轻链可变区基因序列进行比较及分析。结果损害组可变区的互补决定区(CDRS)R(replacement)突变比例(7·57±3·40)明显高于无损害组(4·25±1·90)及同组骨架区(FWRS)(3·29±1·25),BJPλ组可变区CDRS的R突变比例(6·64±2·38)明显高于BJPκ组(4·10±2·13)及同组FWRS区(2·91±0·94);损害组中λ亚型的同源型以V3-4最多。结论BJPλ型患者的肾损害发生率高可能与其BJP基因可变区R突变比例高,从而导致其BJP结构及理化活性的改变有关;可能某些亚型BJP较易发生肾小管损害。
Purpose This study of peripheral blood proteins (BJP) plays a major role in the development of renal damage in multiple myeloma (MM). This study sought to investigate the relationship between the variable region of BJP gene and renal tubular dysfunction. Methods The newly diagnosed renal tubular function was significantly damaged and renal biopsy prompted tubulointerstitial nephropathy patients were divided into damage group, long-term diagnosis of BJP positive and tubular function of normal MM patients without damage group, according to BJP is divided into BJPκ Group and BJPλ group. All patients were routinely drawn to extract mononuclear cells from the bone marrow, total RNA was extracted and reverse transcribed into cDNA. The cloned BJP variable region gene was amplified by PCR and sequenced. The sequence of the light chain variable region gene was analyzed by GenBank. Results The ratio of CDRS mutations (7 · 57 ± 3 · 40) in the variable region of the lesion group was significantly higher than that of the non-lesion group (4.25 ± 1.90) and the same group of the skeleton region (FWRS ) (3.29 ± 1.25). The R mutation ratio of CDRS in BJPλ group (6 · 64 ± 2 · 38) was significantly higher than that in BJPκ group (4.10 ± 2.13) and in the same group 2 · 91 ± 0.94). In the lesion group, the homology of λ subtype was the highest in V3-4. Conclusions The high incidence of renal damage in patients with BJPλ may be related to the high ratio of R mutations in the variable region of BJP gene, which leads to the change of BJP structure and physicochemical activity. It may be that some subtypes of BJP are more prone to renal tubular damage.