Emphatically Lymphatic

Colvin, Robert B.

doi:10.1097/01.asn.0000117895.24143.87

Cited by 8 publications

(5 citation statements)

References 10 publications

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“…The contribution of B cells in renal inflammation has always been considered a potential factor [15], but there is also substantial uncertainty regarding the ectopic formation of lymphoid follicle-like aggregates at sites of chronic inflammation [16,17]. Although the number of B cells in renal tissue has been described to be low [18,19,20,21], a prominent accumulation of B cells was reported in MGN [5].…”

Section: Discussionmentioning

confidence: 99%

Depletion of B Lymphocytes in Idiopathic Membranous Glomerulopathy: Results from Patients with Extended Follow-Up

et al. 2013

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Aims: To assess the long-term therapeutic benefit of temporary depletion of B lymphocytes in patients with idiopathic membranous glomerulopathy (MGN) and search for potential predictors of response. Patients and Methods: The patients included had been diagnosed with biopsy-proven MGN in the absence of secondary causes. Estimated glomerular filtration rate should be above 30 ml/min/1.73 m² and 24-hour proteinuria 3 g/day or more. Patients who had been treated with cyclosporine or cytotoxic agents the year prior to study entry were excluded. Depletion of B cells was achieved with rituximab, which was administered intravenously for 4 consecutive weeks. Partial remission was defined as a >50% decrease in proteinuria with absolute proteinuria <3 g/day, while complete remission was defined as a >50% decrease in proteinuria and an absolute protein excretion <0.3 g/day. Results: Twelve patients were studied (4 females/8 males) with a mean age of 51.3 years. No major adverse effects were observed. During a median follow-up time of 48 months, 11/12 (91.6%) patients achieved remission [7/12 (58.3%) complete remission and 4/12 (33.3%) partial remission], while 1 patient did not respond to therapy. Twelve months after therapy, 68.8% (p = 0.003) of cases had achieved partial and 28.4% complete remission. Measurements of lymphocyte subpopulations did not reveal any changes except for the B cell depletion. B cell infiltrates captured per mm³ of renal tissue in the diagnostic biopsy did not correlate with subsequent response. Conclusion: Depletion of B cells in idiopathic MGN was well tolerated and resulted in significant and long-lasting response rates in a series of 12 patients.

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Section: Discussionmentioning

confidence: 99%

Depletion of B Lymphocytes in Idiopathic Membranous Glomerulopathy: Results from Patients with Extended Follow-Up

et al. 2013

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“…However, it is still a matter of debate whether lymphangiogenesis and potential development of lymphoid structures in renal grafts is beneficial or detrimental to clinical outcome. Lymph vessels could be beneficial by mediating the drainage of extravasated fluid and the export of leukocytes [66]–[68]. On the other hand, lymph vessels and additional development of lymphoid structures could also perpetuate the inflammatory response [66], [67], [69]–[71].…”

Section: Discussionmentioning

confidence: 99%

Differential Expression of Proteoglycans in Tissue Remodeling and Lymphangiogenesis after Experimental Renal Transplantation in Rats

et al. 2010

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BackgroundChronic transplant dysfunction explains the majority of late renal allograft loss and is accompanied by extensive tissue remodeling leading to transplant vasculopathy, glomerulosclerosis and interstitial fibrosis. Matrix proteoglycans mediate cell-cell and cell-matrix interactions and play key roles in tissue remodeling. The aim of this study was to characterize differential heparan sulfate proteoglycan and chondroitin sulfate proteoglycan expression in transplant vasculopathy, glomerulosclerosis and interstitial fibrosis in renal allografts with chronic transplant dysfunction.MethodsRenal allografts were transplanted in the Dark Agouti-to-Wistar Furth rat strain combination. Dark Agouti-to-Dark Agouti isografts and non-transplanted Dark Agouti kidneys served as controls. Allograft and isograft recipients were sacrificed 66 and 81 days (mean) after transplantation, respectively. Heparan sulfate proteoglycan (collXVIII, perlecan and agrin) and chondroitin sulfate proteoglycan (versican) expression, as well as CD31 and LYVE-1 (vascular and lymphatic endothelium, respectively) expression were (semi-) quantitatively analyzed using immunofluorescence.FindingsArteries with transplant vasculopathy and sclerotic glomeruli in allografts displayed pronounced neo-expression of collXVIII and perlecan. In contrast, in interstitial fibrosis expression of the chondroitin sulfate proteoglycan versican dominated. In the cortical tubular basement membranes in both iso- and allografts, induction of collXVIII was detected. Allografts presented extensive lymphangiogenesis (p<0.01 compared to isografts and non-transplanted controls), which was associated with induced perlecan expression underneath the lymphatic endothelium (p<0.05 and p<0.01 compared to isografts and non-transplanted controls, respectively). Both the magnitude of lymphangiogenesis and perlecan expression correlated with severity of interstitial fibrosis and impaired graft function.InterpretationOur results reveal that changes in the extent of expression and the type of proteoglycans being expressed are tightly associated with tissue remodeling after renal transplantation. Therefore, proteoglycans might be potential targets for clinical intervention in renal chronic transplant dysfunction.

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“…Recent findings of a lymphatic neoangiogenesis in renal transplants raise questions about its pathogenic and prog- nostic impact (16). Therefore, we performed a systematic analysis of lymphangiogenesis in protocol biopsies from renal allografts.…”

Section: Discussionmentioning

confidence: 99%

Lymphatic Neoangiogenesis in Human Renal Allografts: Results from Sequential Protocol Biopsies

Stuht¹,

Gwinner²,

Franz³

et al. 2007

American Journal of Transplantation

100

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Neoangiogenesis of lymphatic vessels may be important for the cellular immune response in renal transplants. To determine the prevalence and chronology of lymph vessel proliferation and its relation to cellular infiltrates and allograft function, we analyzed sequential protocol biopsies (n = 162), taken at 6, 12 and 26 weeks after transplantation. Biopsies were stained with an antibody against podoplanin and lymphatic vessel density was quantified per square millimeter.The prevalence of lymph vessel-positive biopsies and the lymph vessel density were similar at 6, 12 and 26 weeks after transplantation. Biopsies with acute cellular rejection showed no significantly different lymph vessel density compared to those below the threshold for acute rejection or chronic allograft nephropathy. While lymphatic neoangiogenesis was equally prevalent in biopsies with and without infiltrates, the lymph vessel density was significantly higher in areas with cellular infiltrates than in areas without. Graft function at 1 year after transplantation was better in cases with lymph vessels in their infiltrates compared to cases with lymph vessel-free infiltrates. In conclusion, lymphangiogenesis not only shows a clear association with cellular infiltrates but might also have an impact on the pathogenicity of these cellular infiltrates.

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Emphatically Lymphatic

Cited by 8 publications

References 10 publications

Depletion of B Lymphocytes in Idiopathic Membranous Glomerulopathy: Results from Patients with Extended Follow-Up

Depletion of B Lymphocytes in Idiopathic Membranous Glomerulopathy: Results from Patients with Extended Follow-Up

Differential Expression of Proteoglycans in Tissue Remodeling and Lymphangiogenesis after Experimental Renal Transplantation in Rats

Lymphatic Neoangiogenesis in Human Renal Allografts: Results from Sequential Protocol Biopsies

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