The role of angiotensin II type 1 receptor-activating antibodies in patients with lupus nephritis

Xiong, Jun; Yang, Hua; Zhu, Fan; Wang, Y.

doi:10.1111/ijcp.12242

Cited by 18 publications

(9 citation statements)

References 9 publications

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“…The mechanisms that support the production of anti‐LG3, anti‐AT1R and antivimentin antibodies in patients awaiting a renal transplantation also remain ill characterized. Although other studies have reported an association between anti‐AT1R, lupus erythematosus and systemic sclerosis , we did not find an association between the autoantibodies we studied and autoimmune diseases. This conclusion, however, is limited by the small number of patients with autoimmune diseases (n = 8) included in the present cohort.…”

Section: Discussioncontrasting

confidence: 99%

Anti-LG3 Antibodies Aggravate Renal Ischemia–Reperfusion Injury and Long-Term Renal Allograft Dysfunction

Yang

Dieudé

Hamelin

et al. 2016

American Journal of Transplantation

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Pretransplant autoantibodies to LG3 and angiotensin II type 1 receptors (AT1R) are associated with acute rejection in kidney transplant recipients, whereas antivimentin autoantibodies participate in heart transplant rejection. Ischemia-reperfusion injury (IRI) can modify self-antigenic targets. We hypothesized that ischemia-reperfusion creates permissive conditions for autoantibodies to interact with their antigenic targets and leads to enhanced renal damage and dysfunction. In 172 kidney transplant recipients, we found that pretransplant anti-LG3 antibodies were associated with an increased risk of delayed graft function (DGF). Pretransplant anti-LG3 antibodies are inversely associated with graft function at 1 year after transplantation in patients who experienced DGF, independent of rejection. Pretransplant anti-AT1R and antivimentin were not associated with DGF or its functional outcome. In a model of renal IRI in mice, passive transfer of anti-LG3 IgG led to enhanced dysfunction and microvascular injury compared with passive transfer with control IgG. Passive transfer of anti-LG3 antibodies also favored intrarenal microvascular complement activation, microvascular rarefaction and fibrosis after IRI. Our results suggest that anti-LG3 antibodies are novel aggravating factors for renal IRI. These results provide novel insights into the pathways that modulate the severity of renal injury at the time of transplantation and their impact on long-term outcomes.

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Section: Discussioncontrasting

confidence: 99%

Anti-LG3 Antibodies Aggravate Renal Ischemia–Reperfusion Injury and Long-Term Renal Allograft Dysfunction

Yang

Dieudé

Hamelin

et al. 2016

American Journal of Transplantation

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“…18,19,34 A previous report that studied AT1R-AAs in 89 Chinese LN patients reported an AT1R-AA prevalence of 66.3% that varied according to the presence of immunosuppressive treatment. 28 We found an AT1R-AA prevalence of 54.2% in active biopsy-proven LN, 15% in patients with inactive disease and 7% in healthy kidney donors.…”

Section: Discussionmentioning

confidence: 58%

“…In 2013, Xiong et al. 28 reported an AT1R-AA positivity of 66.3% in LN patients. Recently, a small study in the transplantation field reported a higher prevalence of subintimal fibrosis in the renal allografts of AT1R-AA-positive patients.…”

Section: Introductionmentioning

confidence: 99%

Angiotensin II receptor agonist antibodies are associated with microvascular damage in lupus nephritis

Mejía-Vilet

López-Hernández

Santander-Velez

et al. 2020

Lupus

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Angiotensin II type 1 receptor agonist antibodies (AT1R-AAs) have been associated with hypertension, atherosclerosis and vascular inflammation in human diseases. The aim of the study was to evaluate the prevalence of AT1R-AAs in active lupus nephritis (LN) patients and their association with vascular damage. One hundred and seven active LN patients underwent a complete clinical examination, measurement of AT1R-AAs, ambulatory blood pressure monitoring, carotid intima-media thickness measurement and morphometric analysis of subintimal fibrosis and medial hyperplasia of the vessels in the kidney tissue. Plasma AT1R-AAs were positive in 58 (54.2%) patients. The Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score, complement C3 and C4 levels and titers of anti-dsDNA antibodies were higher in the group with positive AT1R-AAs compared with those with negative AT1R-AAs. The AT1R-AA titers correlated with anti-dsDNA antibody titers and with complement C3 and C4 serum levels. In the kidney biopsy, the percentage of subintimal fibrosis and the area of medial hyperplasia were greater in the AT1R-AA-positive patients. No differences in arterial pressure, carotid intima-media thickness and response to therapy were detected. In conclusion, AT1R-AAs are prevalent in active LN patients and are associated with histologic features of microvascular damage.

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“…For example, agonistic autoantibodies specific for the angiotensin II type I receptor (AT1R-AA), which have been identified in hypertensive individuals 52–57 , are present in some patients with SLE. A small clinical study revealed that SLE patients who tested positive for the AT1R-AA had higher blood pressure than those that were negative for the autoantibody 58 . In addition, autoantibodies directed against endothelial cells are present in up to 80% of patients with SLE, depending on the cohort 59–61 .…”

Section: Discussionmentioning

confidence: 99%

Plasma Cell Depletion Attenuates Hypertension in an Experimental Model of Autoimmune Disease

et al. 2018

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Numerous studies show a direct relation between circulating autoantibodies, characteristic of systemic autoimmune disorders, and primary hypertension in humans. Whether these autoantibodies mechanistically contribute to the development of hypertension remains unclear. Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder characterized by aberrant immunoglobulin production, notably pathogenic autoantibodies, and is associated with prevalent hypertension, renal injury, and cardiovascular disease. Because plasma cells produce the majority of serum immunoglobulins and are the primary source of autoantibodies in SLE, we hypothesized that plasma cell depletion using the proteasome inhibitor bortezomib would lower autoantibody production and attenuate hypertension. Thirty-week-old female SLE (NZBWF1) and control (NZW [New Zealand White]) mice were injected IV with vehicle (0.9% saline) or bortezomib (0.75 mg/kg) twice weekly for 4 weeks. Bortezomib treatment significantly lowered the percentage of bone marrow plasma cells in SLE mice. Total plasma IgG and anti-dsDNA IgG levels were higher in SLE mice compared with control mice but were lowered by bortezomib treatment. Mean arterial pressure (mm Hg) measured in conscious mice by carotid artery catheter was higher in SLE mice than in control mice, but mean arterial pressure was significantly lower in bortezomib-treated SLE mice. Bortezomib also attenuated renal injury, as assessed by albuminuria and glomerulosclerosis, and reduced glomerular immunoglobulin deposition and B and T lymphocytes infiltration into the kidneys. Taken together, these data show that the production of autoantibodies by plasma cells mechanistically contributes to autoimmune-associated hypertension and suggests a potential role for patients with primary hypertension who have increased circulating immunoglobulins.

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The role of angiotensin II type 1 receptor-activating antibodies in patients with lupus nephritis

Cited by 18 publications

References 9 publications

Anti-LG3 Antibodies Aggravate Renal Ischemia–Reperfusion Injury and Long-Term Renal Allograft Dysfunction

Anti-LG3 Antibodies Aggravate Renal Ischemia–Reperfusion Injury and Long-Term Renal Allograft Dysfunction

Angiotensin II receptor agonist antibodies are associated with microvascular damage in lupus nephritis

Plasma Cell Depletion Attenuates Hypertension in an Experimental Model of Autoimmune Disease

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