Immunohistochemical detection of intravascular platelet microthrombi in patients with lupus nephritis and anti-phospholipid antibodies

Galindo, María; Gonzalo, Elena Sierra; Martínez-Vidal, María Paz; Montes, Santiago; Redondo, Natalia; Santiago, Begoña; Loza, Estíbaliz; Pablos, José L.

doi:10.1093/rheumatology/kep152

Cited by 27 publications

(14 citation statements)

References 26 publications

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“…It is more prevalent in patients with aPL, consistent with previous reports [13]. Moreover, microthrombosis correlates with higher macrophagic infiltration as a marker of inflammatory activity but not with C4d deposition.…”

Section: Discussionsupporting

confidence: 91%

“…Acute thrombosis in LN, as detected with routine histology, is rarely observed, possibly because of its relatively sparse presence and the small size of tissue samples obtained with renal biopsy. Other chronic, nonspecific vascular occlusive histologic lesions may relate to older age and cardiovascular risk factors associated with arteriosclerotic disease, even in patients without aPLs (antiphospholipid antibodies) [13]. This type of chronic occlusive vascular lesions has been associated with a worse renal-function outcome.…”

Section: Introductionmentioning

confidence: 99%

“…This type of chronic occlusive vascular lesions has been associated with a worse renal-function outcome. Immunohistochemical detection of CD61 + intravascular platelets in SLE renal biopsies increases the sensitivity to detect microthrombosis and reveals a high prevalence of microthrombotic lesions in either aPL-negative or -positive LN patients [13]. Whether microthrombotic lesions are a consequence of renal inflammation or independently contribute to renal damage is unclear [10-12].…”

Section: Introductionmentioning

confidence: 99%

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Clinicopathologic correlations of renal microthrombosis and inflammatory markers in proliferative lupus nephritis

Gonzalo

Toldos²,

Martínez-Vidal³

et al. 2012

Arthritis Res Ther

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IntroductionMicrothrombosis is often observed in lupus nephritis (LN) lesions, but its clinical significance is unknown. We evaluated the clinicopathologic correlations of renal microthrombosis and inflammatory markers in LN.MethodsKidney biopsies from 58 patients with systemic lupus erythematosus (SLE) proliferative nephritis were analyzed with immunohistochemistry (IHC) for intravascular platelet aggregates (CD61), macrophagic infiltration (CD68), and activated complement deposition (C4d). Clinical data at the time of kidney biopsy and follow-up were analyzed with regard to pathologic IHC data.ResultsMicrothrombosis was present in 52% of the tissues. It was significantly more prevalent in patients with antiphospholipid antibodies (aPLs) (62% versus 42%). The presence of microthrombosis significantly correlated with higher macrophagic infiltration. Macrophagic infiltration but not microthrombosis was significantly correlated with C4d deposition. Only macrophagic infiltration showed a correlation with SLE and renal activity (proteinuria and active sediment), whereas neither the presence of CD61+ microthrombi nor the extent of C4d deposition correlated with LN severity or outcome.ConclusionsMicrothrombosis is associated with higher macrophagic infiltration in LN but does not seem to increase independently the severity of renal damage. Macrophagic infiltration was the best marker of SLE and renal activity in this LN series.

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Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Clinicopathologic correlations of renal microthrombosis and inflammatory markers in proliferative lupus nephritis

Gonzalo

Toldos²,

Martínez-Vidal³

et al. 2012

Arthritis Res Ther

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“…The platelet staining here corresponds in large part with that seen in other situations. 18 Other arterial and arteriolar lesions of IgAN have been reported as being associated with other clinical and histologic poor prognostic factors 5,19,20 and even potentially independently associated with the degradation of renal function. 21 In our study, both fibrinoid and organized TMA, as well as other vascular lesions, particularly arteriolar lumen size, were significant on univariate analysis (Table 4).…”

Section: Discussionmentioning

confidence: 99%

A Clinicopathologic Study of Thrombotic Microangiopathy in IgA Nephropathy

Karoui

Hill²,

Karras³

et al. 2012

Journal of the American Society of Nephrology

121

105

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Thrombotic microangiopathy (TMA) occurs in IgA nephropathy, but its clinical significance is not well described. We retrospectively examined a series of 128 patients diagnosed with IgA nephropathy between 2002 and 2008 who had a mean follow-up of 44627 months. In our series, 53% presented with lesions of TMA, acute or organized, in arteries and/or arterioles. Among patients with TMA, 4% were normotensive, 25% had controlled hypertension, and 71% had uncontrolled hypertension. Of those with uncontrolled hypertension, 26% had malignant hypertension. Histologically, the group with TMA had a significantly greater percentage of sclerotic glomeruli and worse tubulointerstitial fibrosis than those of the group without TMA. However, a significant minority of patients had near-normal histology, with minimal tubular atrophy (20%) and/or ,20% interstitial fibrosis (24%). TMA rarely occurred in the absence of significant proteinuria. During follow-up, a doubling of serum creatinine or ESRD occurred in all patients with laboratory evidence of TMA, in 42% of those with morphologic evidence but no laboratory evidence of TMA, and in 11% of those without TMA. In summary, lesions of TMA are frequent in IgA nephropathy and may occur in normotensive patients with near-normal renal histology. Although the pathophysiologic mechanisms involved remain undetermined, the current study rules out severe hypertension or advanced renal disease as sole causes.

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“…In animal models of antiphospholipid syndrome (APS), activation of the complement system is necessary for the development of fetal loss and thrombosis (14, 15). Besides routine histological methods (16), immunohistochemistry (IHC) detection of platelet aggregates on kidney sections increases the sensitivity to detect acute microthrombosis (17, 18). However, whether microthrombotic lesions are a consequence of renal inflammation or independently contribute to renal damage is unclear (5, 16, 19).…”

Section: Introductionmentioning

confidence: 99%

Microthrombotic Renal Vascular Lesions Are Associated to Increased Renal Inflammatory Infiltration in Murine Lupus Nephritis

et al. 2018

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Background: Vascular microthrombotic lesions in lupus nephritis with or without antiphospholipid antibodies may relate to worse renal outcomes. Whether microthrombotic lesions are a consequence of renal inflammation or independently contribute to renal damage is unclear. Our aim was to investigate the relationship between microthrombotic renal vascular lesions and nephritis progression in MRL/lpr mice.Methods: MRL/lpr mice were analyzed for the presence of renal microvascular, glomerular and tubulointerstitial lesions and the effect of anti-aggregation (aspirin or clopidogrel) and dexamethasone on renal clinical and pathological manifestations was evaluated. Intravascular platelet aggregates (CD41), peri- (F4/80), and intraglomerular (Mac-2) macrophage infiltration, and C3 deposition were quantified by immunohistochemistry. Renal function was assessed by measuring proteinuria, and serum levels of creatinine and albumin. Anti-dsDNA and anti-cardiolipin antibodies, and thromboxane B2 levels were quantified by ELISA.Results: Frequency of microthrombotic renal lesions in MRL/lpr mice was high and was associated with immune-mediated renal damage. Proteinuria positively correlated with glomerular macrophage infiltration and was higher in mice with proliferative glomerular lesions. All mice had detectable anti-dsDNA and anti-cardiolipin IgG, regardless the presence of microthrombosis. Proteinuria and glomerular macrophage infiltration were significantly reduced in all treatment groups. Dexamethasone and platelet anti-aggregation similarly reduced glomerular damage and inflammation, but only platelet anti-aggregation significantly reduced anti-cardiolipin antibodies, renal complement deposition and thromboxane B2 levels.Conclusions: Platelet anti-aggregation reduced renal inflammatory damage, renal complement deposition, anti-cardiolipin antibodies, and thromboxane B2 levels and in MRL/lpr mice, suggesting that platelet activation has a pathogenic effect on immune-mediated nephritis. Our results point to MRL/lpr mice with lupus nephritis as an appropriate model to analyze the potential impact of anti-thrombotic intervention on renal inflammation.

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Immunohistochemical detection of intravascular platelet microthrombi in patients with lupus nephritis and anti-phospholipid antibodies

Cited by 27 publications

References 26 publications

Clinicopathologic correlations of renal microthrombosis and inflammatory markers in proliferative lupus nephritis

Clinicopathologic correlations of renal microthrombosis and inflammatory markers in proliferative lupus nephritis

A Clinicopathologic Study of Thrombotic Microangiopathy in IgA Nephropathy

Microthrombotic Renal Vascular Lesions Are Associated to Increased Renal Inflammatory Infiltration in Murine Lupus Nephritis

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