IgA肾病肾脏淋巴管新生和异位淋巴结形成与病变程度、预后相关
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摘要
IgA肾病(IgAN)因其肾小球系膜区IgA的沉积而命名,是全世界最常见的一类肾小球疾病。按照现有牛津分级标准,肾小球出现系膜细胞增生；节段性肾小球硬化(或粘连)；毛细血管内增生和肾小管萎缩/间质纤维化与IgAN肾脏预后相关。有关慢性肾脏病中肾脏淋巴管新生和异位淋巴结形成的研究在最近几年开始受到关注,但是它们在慢性肾脏病中特别是IgAN中的确切角色还不清楚,为此我们依托同济医院肾病实验室肾穿标本库的资源设计了前瞻性的实验,来明确肾脏淋巴管新生和异位淋巴结形成与肾脏病变和预后的关系。152例肾穿之前未经激素和免疫抑制剂治疗的IgAN患者按照相关纳入和排除标准作为研究对象。34个月的随访期后,72例患者有着完整的预后资料,其中63例患者在肾穿刺后进行了正规的激素治疗。我们采用检测每一例患者肾组织内新生淋巴管、异位淋巴结以及CD68+,DC-SIGN+,CD4+,CD8+,CD20+炎症细胞,并对它们的密度进行统计。我们发现IgAN患者肾间质新生淋巴管分布于肾小球周围和病变的肾间质部位。新生淋巴管参与不同类型炎症细胞的转运。新生淋巴管的密度与血肌酐、蛋白尿以及间质炎症细胞评分、小管萎缩/间质纤维化评分、小血管内膜增厚、小血管玻璃样变程度关系密切。随访期内激素治疗“敏感组”肾间质新生淋巴管和DC-SIGN+树突状细胞密度显著低于“不敏感组”,肾间质淋巴管密度和CD68+,DC-SIGN+,CD4+,CD8+,CD20+细胞密度与随访期内血清肌酐进展密切相关。多元回归分析显示肾间质淋巴管密度高是IgAN患者血肌酐进展的独立危险因素。我们还发现IgAN肾组织异位淋巴结结构内CD20+B细胞位于中央,CD4+、CD8+T细胞分布于外周,DC-SIGN+树突状细胞和CD68+单核细胞,散在分布于异位淋巴结,D2-40阳性淋巴管分布于异位淋巴结结构的周围或中央。细胞成分分泌多种促炎症因子,T淋巴细胞处于活化状态,散在少量分泌IgG和IgM的浆细胞。肾间质异位淋巴结结构的越多的患者蛋白尿水平、血肌酐水平、有新月体、间质和小血管损伤较重的比例高于肾间质异位淋巴结结构较少的患者。随访期内肾脏异位淋巴结较多的患者血肌酐进展的比例较大。IgAN患者肾脏新生淋巴管和异位淋巴结的出现反映了肾脏局部的炎症反应的活化状态,它们可能参与IgAN患者肾脏损伤和进展。
第一部分IgA肾病间质炎症细胞评分与病变程度、预后的关系
目的探讨间质炎症细胞浸润评分与IgAN病变程度和预后间的关联度
方法按照纳入和排除标准选取入组患者,纳入组IgAN患者肾病病变按牛津分级进行评分,对间质炎症细胞的浸润程度评分。比较不同炎症细胞评分的IgAN患者的临床、病理指标和随访期内血肌酐进展的比例之间的差异。对CD45, IL-1β,TNFα,IFN-γ和IL-17进行免疫组化染色。
结果间质炎症细胞评分与IgAN患者肾小球C3、IgG沉积、蛋白尿和血肌酐水平、系膜增生程度、肾小球有新月体的比例、间质和小血管病变程度关系密切。间质炎症细胞与炎症因子在连续切片呈现共定位。在随访数据中,间质炎症细胞评分高的患者,34月后血肌酐进展的比例较高。
结论炎症细胞浸润程度反映了整个肾脏的炎症反应水平。间质炎症细胞可能通过分泌炎症因子参与IgAN的进展。间质炎症细胞评分较高的IgAN患者预后不良的风险大。
第二部分IgA肾病肾间质不同类型炎症细胞与病变程度、预后的关系
目的探讨不同类型间质炎症细胞浸润与IgAN病变程度间的关联度
方法按照纳入和排除标准选取入组患者,纳入组IgAN患者肾病病变按牛津分级进行评分。选取同一片号的连续切片分别进行CD68+,DC-SIGN+,CD4+,CD8+,CD20+免疫组化染色。统计不同片号各种类型炎症细胞的密度。对不同类型炎症细胞的密度与IgAN患者的临床、病理指标和随访期内血肌酐进展的比例之间的进行相关性分析。
结果IgAN患者肾间质CD68+,DC-SIGN+,CD4+,CD8+,CD20+炎症细胞分布于肾小球周围和病变的肾间质部位,免疫荧光双标显示这些炎症细胞是活化的,部分炎症细胞还分泌炎症因子。CD68+,DC-SIGN+,CD4+,CD8+,CD20+炎症细胞的密度与血肌酐、蛋白尿以及间质炎症细胞评分、小管萎缩/间质纤维化评分、小血管内膜增厚、小血管玻璃样变程度关系密切。随访期内激素治疗“敏感组”肾间质DC-SIGN+细胞的密度显著低于“不敏感组”,肌酐“进展组”肾间质CD68+,DC-SIGN+,CD4+, CD8+,CD20+炎症细胞的密度显著高于“稳定组”。
结论间质浸润的炎症细胞的密度与IgAN患者临床指标、肾脏病变程度和预后密切相关,因而反映了IgAN的肾脏病变程度,另一方面间质浸润的炎症细胞因其活化状态可能直接或间接加重IgAN的损伤,参与IgAN的进展。IgAN肾间质DC-SIGN+细胞密度与患者对激素的敏感程度相关。
第三部分IgAN患者肾间质新生淋巴管与病变程度、预后的关系
目的探讨IgAN患者肾组织中新生淋巴管与IgAN病变程度间的关联度
方法按照纳入和排除标准选取入组患者,纳入组IgAN患者肾病病变按牛津分级进行评分。选取同一片号的连续切片分别进行D2-40和CD31免疫组化染色。统计不同片号间质新生淋巴管和间质微血管的密度。对新生淋巴管的密度与IgAN患者的临床、病理指标和随访期内血肌酐进展的比例之间的进行相关性分析。
结果IgAN患者肾间质新生淋巴管分布于肾小球周围和病变的肾间质部位。新生淋巴管参与不同类型炎症细胞的转运。新生淋巴管的密度与血肌酐、蛋白尿以及间质炎症细胞评分、小管萎缩/间质纤维化评分、小血管内膜增厚、小血管玻璃样变程度关系密切。随访期内激素治疗“敏感组”肾间质新生淋巴管的密度显著低于“不敏感组”,肌酐“进展组”肾间质淋巴管密度显著高于“稳定组”。多元回归分析显示肾间质淋巴管密度高是IgAN患者血肌酐进展的独立危险因素。
结论新生淋巴管的密度与IgAN患者临床指标、肾脏病变程度和预后密切相关,因而反映了IgAN的肾脏病变程度,另一方面作为炎症细胞的转运通道,新生淋巴管可能直接参与IgAN的肾脏损伤和肾功能进展。IgAN肾间质新生淋巴管密度与患者对激素的敏感程度相关。
第四部分IgAN患者肾间质异位淋巴结与病变程度、预后的关系
目的探讨IgAN患者肾组织异位淋巴结与IgAN病变程度间的关联度
方法按照纳入和排除标准选取入组患者,纳入组IgAN患者肾病病变按牛津分级进行评分。对异位淋巴结的数量进行评分。分析异位淋巴结的密度等级与IgAN患者的临床、病理指标和随访期内血肌酐进展的比例之间的相关性。检测异位淋巴结内CD68+,DC-SIGN+,CD4+,CD8+,CD20+,CD45+,CD138+炎症细胞、淋巴管和炎症因子的表达。
结果CD20+B细胞位于中央,CD4+、CD8+T细胞分布于外周,DC-SIGN+树突状细胞和CD68+单核细胞,散在分布于异位淋巴结,淋巴管分布于异位淋巴结结构的周围或中央。肾间质异位淋巴结结构的越多的患者蛋白尿水平、血肌酐水平、有新月体、间质和小血管损伤较重的比例高于肾间质异位淋巴结结构较少的患者。34个月随访期内异位淋巴结结构的越多的患者血清肌酐进展的比例高于肾间质异位淋巴结结构较少的患者。IgAN肾组织异位淋巴结结构内细胞成分分泌多种促炎症因子,T淋巴细胞处于活化状态,散在少量分泌IgG和IgM的浆细胞。
结论肾脏异位淋巴结内B淋巴细胞与活化的T细胞、DC-SIGN+的树突状细胞和淋巴管相伴存在,还包含有产生抗体的浆细胞,是肾脏局部的炎症反应灶,可能参与IgAN的进展。肾脏异位淋巴结与IgAN肾脏病变程度密切相关,肾脏异位淋巴结较多的患者随访期内血肌酐进展的比例较大。
IgA Nephropathy(IgAN), which features IgA deposition in the glomerular mesangium, is the most common form of primary glomerulonephritis worldwide.Previous studies have identified histologic features such as mesangial hypercellularity,segmental glomerulosclerosis, endocapillary hypercellularity and tubular atrophy/interstitial fibrosiswere associated with renal outcome of IgAN according to the Oxford classification.Lymphangiogenesis and tertiary lymphoid organs formation were newly identified in the kidney of patients with chronic kidney disease(CKD). However, there is not much information about the exact role in the progression of IgAN.We performed this prospective study to determine the realtionship between these two" new players" and the renal lesion and prognosis of IgAN.We selected152IgAN paitents who did not receive glucocorticoid or immunosuppressant treatment before renal biopsy.72patients had integrated outcome data after34months follow-up.63patient receive regular glucocorticoids treatment were finally left in the analysis involve prognosis.The density of the density of renal newly formed lymphatic vessels(LVD) and inflammatory cells and the grade of tertiary lymphoid organs(TLO) were evaluated. We found that renal newly formed lymphatic vessels served as "transport channel" of inflammatory cells,the LVD in IgAN renal tissue was correlated with the density of CD68+, DC-SIGN+, CD4+, CD8+, CD20+cells and the interstitial and arterial lesions of kidney and also sensitivity to glucocorticoid treatment.A linear regression analysis revealed the LVD was a significant predictor of an increase of serum creatinine34months after the biopsy. CD68+, DC-SIGN+, CD4+, CD8+, CD20+,CD45RO+,CD138+cells,lymphatic vessels and inflammatory cytokines were found in renal TLO.Patients with more TLO suffered decreased renal function, heavy proteinuria, severe interstitial and arterial lesions.TLO were also associated with progression of IgAN after34months follow up.In conclusion,renal lymphangiogenesis and tertiary lymphoid organs formation reflected the status of the intrarenal inflammatory response,they might also paly an active role in renal lesion by affecting the severity of local immunity. In the future,there will be new strategy to slow the progression of IgAN depending on more detailed mechanism of lymphangiogenesis and TLO.
Part I The grade of renal interstitial inflammatory cells were correlated with the renal lesion and prognosis of IgAN patients
Objectives To determine whether the grade of renal inflammatory cells are correlated with the renal lesion of IgAN.
Methods The renal lesion of IgAN was scored by Oxford Classification. The relationship between the grade of interstitial inflammatory cells and renal lesion was evaluated. Immunohistochemistrial staining for CD45, IL-1β,TNF α,IFN-γ and IL-17were performed to detect inflammatory cells and inflammatory cytokines in renal biopsy tissues from IgAN patients. Sixty-three patients with IgAN were followed for34months.
Results The grade of inflammatory cells in renal interstitium were closely related to the decreased renal function, heavy proteinuria, severe interstitial and arterial lesions in IgAN kidneys. Patients with higher grade of inflammatory cells sufferred higher risk to progress during34months. CD45+cells colocated with inflammatory cytokines suggested inflammatory cells may take part in the progression of IgAN..
Conclusion The grade of interstitial inflammatory cells can be used as reliable parameter to evaluate the renal lesion and prognosis of IgAN.
Part II Different types of renal interstitial inflammatory cells were correlated with the renal lesion and prognosis of IgAN patients
Objectives To determine the relationship between the density of different types inflammatory cells and the renal lesion of IgAN.
Methods Immunohistochemistrial staining for CD68, DC-SIGN, CD4, CD8and CD20 were performed to detect macrophages, dendritic cells, T-helper cells, cytotoxic T cells, B cells respectively in renal biopsy tissues from152adult patients with IgAN. The relationship between inflammatory cells and renal lesion was evaluated. Sixty-three patients with IgAN were followed for34months.
Results The density of CD68+, DC-SIGN+, CD4+, CD8+, and CD20+cells in renal interstitium were closely related to the decreased renal function, heavy proteinuria, severe interstitial and arterial lesions in IgAN kidneys.The patients in the severe group contained more CD68+, DC-SIGN+, CD4+, CD8+, and CD20+cells in renal interstitium.The patients who are not sensitive to glucocorticoid treatment had more DC-SIGN+cells in renal interstitium.
Conclusions Interstitial infiltrated inflammatory cells reflected the status of the intrarenal inflammatory response, which probably aggravated the renal lesion, and in turn, accelerated the IgAN progression.The sensitivity to glucocorticoid treatment was correlated with density of DC-SIGN+cells
Part Ⅲ Renal interstitial newly formed lymphatic vessels were correlated with the renal lesion and prognosis of IgAN patients
Objectives To explore the exact role of newly formed lymphatic vessels in cohort of IgAN patients.
Methods152patients with biopsy-proven IgAN were selected. The lymphatic vessels in the renal of examined by IHC. The relationship between the lymphatic vessels density and renal lesion was evaluated.in152IgAN patients.A Follow-up was performed for outpatients by telephone.
Results The LVD in IgAN renal tissue was correlated with the density of CD68+, DC-SIGN+, CD4+, CD8+, CD20+cells and the lesions of kidney.A linear regression analysis revealed the density of lymph vessels was a significant predictor of an increase of serum creatinine34months after the biopsy.
Conclusions Lymphangiogenesis reflected the status of the intrarenal inflammatory response, their density could be served as a risk factor for IgAN progression.As they served as "transport channel" of inflammatory cells,they might also paly an active role in renal lesion.
Part IV Renal interstitial tertiary lymphoid organs were correlated with the renal lesion and prognosis of IgAN patients
Objectives To determine whether interstitial TLO formation are correlated with the renal lesion and progression of IgAN.
Methods The relationship between TLO and renal lesion was evaluated.in152IgAN patients.CD68,DC-SIGN,CD4,CD8,CD20,CD45,CD138,D2-40,IL-1β,TNF-α,IFN-γ and IL-17were examined in TLO.Sixty-three IgAN patients were followed for30months.
Results CD68+, DC-SIGN+, CD4+, CD8+, CD20+,CD45+,CD138+cells,lymphatic vessels and inflammatory cytokines were found in renal TLO.Patients with more TLO suffered decreased renal function, heavy proteinuria, severe interstitial and arterial lesions.TLO were associated with the progression of IgAN after30months follow up.
Conclusions TLO formation reflected the status of the intrarenal inflammatory response, which probably aggravated the renal lesion of IgAN. They could be served as a risk factor for IgAN progression.
第一部分IgA肾病间质炎症细胞评分与病变程度、预后的关系
目的探讨间质炎症细胞浸润评分与IgAN病变程度和预后间的关联度
方法按照纳入和排除标准选取入组患者,纳入组IgAN患者肾病病变按牛津分级进行评分,对间质炎症细胞的浸润程度评分。比较不同炎症细胞评分的IgAN患者的临床、病理指标和随访期内血肌酐进展的比例之间的差异。对CD45, IL-1β,TNFα,IFN-γ和IL-17进行免疫组化染色。
结果间质炎症细胞评分与IgAN患者肾小球C3、IgG沉积、蛋白尿和血肌酐水平、系膜增生程度、肾小球有新月体的比例、间质和小血管病变程度关系密切。间质炎症细胞与炎症因子在连续切片呈现共定位。在随访数据中,间质炎症细胞评分高的患者,34月后血肌酐进展的比例较高。
结论炎症细胞浸润程度反映了整个肾脏的炎症反应水平。间质炎症细胞可能通过分泌炎症因子参与IgAN的进展。间质炎症细胞评分较高的IgAN患者预后不良的风险大。
第二部分IgA肾病肾间质不同类型炎症细胞与病变程度、预后的关系
目的探讨不同类型间质炎症细胞浸润与IgAN病变程度间的关联度
方法按照纳入和排除标准选取入组患者,纳入组IgAN患者肾病病变按牛津分级进行评分。选取同一片号的连续切片分别进行CD68+,DC-SIGN+,CD4+,CD8+,CD20+免疫组化染色。统计不同片号各种类型炎症细胞的密度。对不同类型炎症细胞的密度与IgAN患者的临床、病理指标和随访期内血肌酐进展的比例之间的进行相关性分析。
结果IgAN患者肾间质CD68+,DC-SIGN+,CD4+,CD8+,CD20+炎症细胞分布于肾小球周围和病变的肾间质部位,免疫荧光双标显示这些炎症细胞是活化的,部分炎症细胞还分泌炎症因子。CD68+,DC-SIGN+,CD4+,CD8+,CD20+炎症细胞的密度与血肌酐、蛋白尿以及间质炎症细胞评分、小管萎缩/间质纤维化评分、小血管内膜增厚、小血管玻璃样变程度关系密切。随访期内激素治疗“敏感组”肾间质DC-SIGN+细胞的密度显著低于“不敏感组”,肌酐“进展组”肾间质CD68+,DC-SIGN+,CD4+, CD8+,CD20+炎症细胞的密度显著高于“稳定组”。
结论间质浸润的炎症细胞的密度与IgAN患者临床指标、肾脏病变程度和预后密切相关,因而反映了IgAN的肾脏病变程度,另一方面间质浸润的炎症细胞因其活化状态可能直接或间接加重IgAN的损伤,参与IgAN的进展。IgAN肾间质DC-SIGN+细胞密度与患者对激素的敏感程度相关。
第三部分IgAN患者肾间质新生淋巴管与病变程度、预后的关系
目的探讨IgAN患者肾组织中新生淋巴管与IgAN病变程度间的关联度
方法按照纳入和排除标准选取入组患者,纳入组IgAN患者肾病病变按牛津分级进行评分。选取同一片号的连续切片分别进行D2-40和CD31免疫组化染色。统计不同片号间质新生淋巴管和间质微血管的密度。对新生淋巴管的密度与IgAN患者的临床、病理指标和随访期内血肌酐进展的比例之间的进行相关性分析。
结果IgAN患者肾间质新生淋巴管分布于肾小球周围和病变的肾间质部位。新生淋巴管参与不同类型炎症细胞的转运。新生淋巴管的密度与血肌酐、蛋白尿以及间质炎症细胞评分、小管萎缩/间质纤维化评分、小血管内膜增厚、小血管玻璃样变程度关系密切。随访期内激素治疗“敏感组”肾间质新生淋巴管的密度显著低于“不敏感组”,肌酐“进展组”肾间质淋巴管密度显著高于“稳定组”。多元回归分析显示肾间质淋巴管密度高是IgAN患者血肌酐进展的独立危险因素。
结论新生淋巴管的密度与IgAN患者临床指标、肾脏病变程度和预后密切相关,因而反映了IgAN的肾脏病变程度,另一方面作为炎症细胞的转运通道,新生淋巴管可能直接参与IgAN的肾脏损伤和肾功能进展。IgAN肾间质新生淋巴管密度与患者对激素的敏感程度相关。
第四部分IgAN患者肾间质异位淋巴结与病变程度、预后的关系
目的探讨IgAN患者肾组织异位淋巴结与IgAN病变程度间的关联度
方法按照纳入和排除标准选取入组患者,纳入组IgAN患者肾病病变按牛津分级进行评分。对异位淋巴结的数量进行评分。分析异位淋巴结的密度等级与IgAN患者的临床、病理指标和随访期内血肌酐进展的比例之间的相关性。检测异位淋巴结内CD68+,DC-SIGN+,CD4+,CD8+,CD20+,CD45+,CD138+炎症细胞、淋巴管和炎症因子的表达。
结果CD20+B细胞位于中央,CD4+、CD8+T细胞分布于外周,DC-SIGN+树突状细胞和CD68+单核细胞,散在分布于异位淋巴结,淋巴管分布于异位淋巴结结构的周围或中央。肾间质异位淋巴结结构的越多的患者蛋白尿水平、血肌酐水平、有新月体、间质和小血管损伤较重的比例高于肾间质异位淋巴结结构较少的患者。34个月随访期内异位淋巴结结构的越多的患者血清肌酐进展的比例高于肾间质异位淋巴结结构较少的患者。IgAN肾组织异位淋巴结结构内细胞成分分泌多种促炎症因子,T淋巴细胞处于活化状态,散在少量分泌IgG和IgM的浆细胞。
结论肾脏异位淋巴结内B淋巴细胞与活化的T细胞、DC-SIGN+的树突状细胞和淋巴管相伴存在,还包含有产生抗体的浆细胞,是肾脏局部的炎症反应灶,可能参与IgAN的进展。肾脏异位淋巴结与IgAN肾脏病变程度密切相关,肾脏异位淋巴结较多的患者随访期内血肌酐进展的比例较大。
IgA Nephropathy(IgAN), which features IgA deposition in the glomerular mesangium, is the most common form of primary glomerulonephritis worldwide.Previous studies have identified histologic features such as mesangial hypercellularity,segmental glomerulosclerosis, endocapillary hypercellularity and tubular atrophy/interstitial fibrosiswere associated with renal outcome of IgAN according to the Oxford classification.Lymphangiogenesis and tertiary lymphoid organs formation were newly identified in the kidney of patients with chronic kidney disease(CKD). However, there is not much information about the exact role in the progression of IgAN.We performed this prospective study to determine the realtionship between these two" new players" and the renal lesion and prognosis of IgAN.We selected152IgAN paitents who did not receive glucocorticoid or immunosuppressant treatment before renal biopsy.72patients had integrated outcome data after34months follow-up.63patient receive regular glucocorticoids treatment were finally left in the analysis involve prognosis.The density of the density of renal newly formed lymphatic vessels(LVD) and inflammatory cells and the grade of tertiary lymphoid organs(TLO) were evaluated. We found that renal newly formed lymphatic vessels served as "transport channel" of inflammatory cells,the LVD in IgAN renal tissue was correlated with the density of CD68+, DC-SIGN+, CD4+, CD8+, CD20+cells and the interstitial and arterial lesions of kidney and also sensitivity to glucocorticoid treatment.A linear regression analysis revealed the LVD was a significant predictor of an increase of serum creatinine34months after the biopsy. CD68+, DC-SIGN+, CD4+, CD8+, CD20+,CD45RO+,CD138+cells,lymphatic vessels and inflammatory cytokines were found in renal TLO.Patients with more TLO suffered decreased renal function, heavy proteinuria, severe interstitial and arterial lesions.TLO were also associated with progression of IgAN after34months follow up.In conclusion,renal lymphangiogenesis and tertiary lymphoid organs formation reflected the status of the intrarenal inflammatory response,they might also paly an active role in renal lesion by affecting the severity of local immunity. In the future,there will be new strategy to slow the progression of IgAN depending on more detailed mechanism of lymphangiogenesis and TLO.
Part I The grade of renal interstitial inflammatory cells were correlated with the renal lesion and prognosis of IgAN patients
Objectives To determine whether the grade of renal inflammatory cells are correlated with the renal lesion of IgAN.
Methods The renal lesion of IgAN was scored by Oxford Classification. The relationship between the grade of interstitial inflammatory cells and renal lesion was evaluated. Immunohistochemistrial staining for CD45, IL-1β,TNF α,IFN-γ and IL-17were performed to detect inflammatory cells and inflammatory cytokines in renal biopsy tissues from IgAN patients. Sixty-three patients with IgAN were followed for34months.
Results The grade of inflammatory cells in renal interstitium were closely related to the decreased renal function, heavy proteinuria, severe interstitial and arterial lesions in IgAN kidneys. Patients with higher grade of inflammatory cells sufferred higher risk to progress during34months. CD45+cells colocated with inflammatory cytokines suggested inflammatory cells may take part in the progression of IgAN..
Conclusion The grade of interstitial inflammatory cells can be used as reliable parameter to evaluate the renal lesion and prognosis of IgAN.
Part II Different types of renal interstitial inflammatory cells were correlated with the renal lesion and prognosis of IgAN patients
Objectives To determine the relationship between the density of different types inflammatory cells and the renal lesion of IgAN.
Methods Immunohistochemistrial staining for CD68, DC-SIGN, CD4, CD8and CD20 were performed to detect macrophages, dendritic cells, T-helper cells, cytotoxic T cells, B cells respectively in renal biopsy tissues from152adult patients with IgAN. The relationship between inflammatory cells and renal lesion was evaluated. Sixty-three patients with IgAN were followed for34months.
Results The density of CD68+, DC-SIGN+, CD4+, CD8+, and CD20+cells in renal interstitium were closely related to the decreased renal function, heavy proteinuria, severe interstitial and arterial lesions in IgAN kidneys.The patients in the severe group contained more CD68+, DC-SIGN+, CD4+, CD8+, and CD20+cells in renal interstitium.The patients who are not sensitive to glucocorticoid treatment had more DC-SIGN+cells in renal interstitium.
Conclusions Interstitial infiltrated inflammatory cells reflected the status of the intrarenal inflammatory response, which probably aggravated the renal lesion, and in turn, accelerated the IgAN progression.The sensitivity to glucocorticoid treatment was correlated with density of DC-SIGN+cells
Part Ⅲ Renal interstitial newly formed lymphatic vessels were correlated with the renal lesion and prognosis of IgAN patients
Objectives To explore the exact role of newly formed lymphatic vessels in cohort of IgAN patients.
Methods152patients with biopsy-proven IgAN were selected. The lymphatic vessels in the renal of examined by IHC. The relationship between the lymphatic vessels density and renal lesion was evaluated.in152IgAN patients.A Follow-up was performed for outpatients by telephone.
Results The LVD in IgAN renal tissue was correlated with the density of CD68+, DC-SIGN+, CD4+, CD8+, CD20+cells and the lesions of kidney.A linear regression analysis revealed the density of lymph vessels was a significant predictor of an increase of serum creatinine34months after the biopsy.
Conclusions Lymphangiogenesis reflected the status of the intrarenal inflammatory response, their density could be served as a risk factor for IgAN progression.As they served as "transport channel" of inflammatory cells,they might also paly an active role in renal lesion.
Part IV Renal interstitial tertiary lymphoid organs were correlated with the renal lesion and prognosis of IgAN patients
Objectives To determine whether interstitial TLO formation are correlated with the renal lesion and progression of IgAN.
Methods The relationship between TLO and renal lesion was evaluated.in152IgAN patients.CD68,DC-SIGN,CD4,CD8,CD20,CD45,CD138,D2-40,IL-1β,TNF-α,IFN-γ and IL-17were examined in TLO.Sixty-three IgAN patients were followed for30months.
Results CD68+, DC-SIGN+, CD4+, CD8+, CD20+,CD45+,CD138+cells,lymphatic vessels and inflammatory cytokines were found in renal TLO.Patients with more TLO suffered decreased renal function, heavy proteinuria, severe interstitial and arterial lesions.TLO were associated with the progression of IgAN after30months follow up.
Conclusions TLO formation reflected the status of the intrarenal inflammatory response, which probably aggravated the renal lesion of IgAN. They could be served as a risk factor for IgAN progression.
引文
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