Department of Nephrology, China-Japan Friendship Hospital, Beijing 100029, P.R. China.
Department of Nephrology, PLA General Hospital, Institute of Nephrology, Beijing Key Laboratory of Kidney Disease, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing 100853, P.R. China.
Biosci Rep. 2019 Oct 30;39(10). doi: 10.1042/BSR20190482.
IgA nephropathy (IgAN) is one of the most common chronic glomerulonephritis. Its etiology and pathogenesis remain unclear. We thus explored the immune repertoire of the B-cell receptor (BCR) and the heavy-chain complementarity-determining region 3 (CDR3) in renal tissue and peripheral blood of IgAN patients.
Total RNAs extracted from renal tissues and peripheral blood of patients and peripheral blood of healthy controls (HCs) were analyzed via high-throughput multiplex PCR sequencing. We amplified and sequenced BCR heavy-chain CDR3 regions to explore repertoire diversity, V/J gene family distribution, CDR3 lengths, BCR heavy-chain variants, consistency between tissue and peripheral blood data, and clones 'shared' by these bodily compartments.
We identified the renal tissue and peripheral blood BCR heavy-chain CDR3 immune repertoires of 15 IgAN patients. Top1 could be more readily cloned from peripheral blood of patients than from controls (P<0.05), the average CDR3 length was significantly shorter in patients than in HCs (P<0.05), the variant frequency of the gene encoding the BCR heavy chain was higher in patients than in HCs (P<0.05), and the BCR variant frequency was highest in IgAN kidney tissue. Preliminary screening for 'shared' clones showed that, in at least 13 patients, the 'ALYFHNSAY', 'ARWGPMYYYMDV', 'ARDQGALNA', and 'ARVDNPADF' CDR3 sequences were evident in peripheral blood samples from patients, but not HCs.
We found that the 'ALYFHNSAY', 'ARWGPMYYYMDV', 'ARDQGALNA', and 'ARVDNPADF' clonal sequences may be useful for noninvasive diagnosis and treatment planning in IgAN.
IgA 肾病（IgAN）是最常见的慢性肾小球肾炎之一。其病因和发病机制尚不清楚。因此，我们探索了 IgAN 患者肾组织和外周血中 B 细胞受体（BCR）和重链互补决定区 3（CDR3）的免疫受体库。
通过高通量多重 PCR 测序分析从患者肾组织和外周血以及健康对照（HC）外周血中提取的总 RNA。我们扩增和测序了 BCR 重链 CDR3 区，以探索 repertoire 多样性、V/J 基因家族分布、CDR3 长度、BCR 重链变体、组织和外周血数据之间的一致性，以及这些体腔共享的克隆。
我们鉴定了 15 例 IgAN 患者的肾组织和外周血 BCR 重链 CDR3 免疫受体库。与 HCs 相比，患者外周血中更容易克隆出 Top1（P<0.05），患者的平均 CDR3 长度明显短于 HCs（P<0.05），编码 BCR 重链的基因变异频率患者高于 HCs（P<0.05），BCR 变异频率在 IgAN 肾组织中最高。对“共享”克隆的初步筛选表明，至少在 13 例患者中，“ALYFHNSAY”、“ARWGPMYYYMDV”、“ARDQGALNA”和“ARVDNPADF”CDR3 序列在患者的外周血样本中存在，但在 HCs 中不存在。
我们发现“ALYFHNSAY”、“ARWGPMYYYMDV”、“ARDQGALNA”和“ARVDNPADF”克隆序列可能有助于 IgAN 的非侵入性诊断和治疗计划。
