IgA anti-ß2 glycoprotein I antibodies: Experience from a large center.

OBJECTIVE: IgG and IgM antibodies directed at ß2-glycoprotein I are included in the classification criteria for the antiphospholipid syndrome (APS) while the IgA antibodies against ß2-glycoprotein I (IgA aß2GPI) are not. Conflicting data about the significance of IgA aß2GPI and APS manifestation can be found and more studies are necessary in order to define the diagnostic value of IgA aß2GPI. In the present article, we investigated the possible role of IgA aß2GPI as marker of APS. METHODS: A cohort of 314 patients with APS and systemic autoimmune disease was investigated for the presence of IgA aß2GPI and its association with clinical manifestation of APS. RESULTS: Eighty-nine patients presented IgA aß2GPI, 68 cases associated with others antiphospholipid antibodies (aPL) and in 21 cases being the only aPL present. In primary APS IgA aß2GPI are highly coincidental with other aPL (92,2%) while most of the isolated IgA aß2GPI were present in the SLE group (16/21). No association between IgA aß2GPI and APS manifestations: thrombosis and pregnancy morbidity was found, while a positive association between IgA aß2GPI and the presence of anti-nDNA, anti-RNP, anti-Sm, anti-SSA, anti-SSB antibodies was encountered. CONCLUSION: Our study does not show association between IgA aß2GPI and APS manifestations and does not support the inclusion of IgA aß2GPI as a classification criteria for APS.

Antiphosphatidylserine/prothrombin antibodies (aPS/PT) as potential markers of antiphospholipid syndrome.

The antiphospholipid antibodies present in antiphospholipid syndrome (APS) are directed at a number of phospholipid-binding proteins: ß2 glycoprotein I (ß2GPI), prothrombin, and so on. Antibodies directed at ß2GPI are accepted as a classification criterion for APS, while the presence of antiprothrombin antibodies is not. In the present article, we investigated the possible role of antiphosphatidylserine/prothrombin antibodies (aPS/PT) as marker of APS on a cohort of 295 individuals with APS (95 primary APS and 45 secondary APS) and APS-related diseases. We found aPS/PT to be highly associated with venous thrombosis (immunoglobulin G [IgG] aPS/PT odds ratio [OR], 7.44; 95% confidence interval [CI], 3.97-13.92 and IgM aPS/PT OR, 2.54; 95% CI, 1.35-4.77) and obstetric abnormalities (IgG aPS/PT OR, 2.37; 95% CI, 1.04-5.43), but not with arterial thrombosis. A very high degree of concordance between the concentration of aPS/PT and lupus anticoagulant activity was demonstrated. Therefore, we support the inclusion of aPS/PT determination as second-level assay to confirm APS classification.

Malnutrition-inflammation syndrome is associated with endothelial dysfunction in peritoneal dialysis patients.

Endothelial dysfunction with atherosclerosis is a recognized complication of uremic patients. The hypoalbuminemia of peritoneal dialysis (PD) patients can induce a hypercoagulable and atherogenic state. In this study, we investigated the role played by malnutrition-inflammation syndrome on endothelial function markers in PD patients. We measured markers of nutrition [normalized protein catabolic rate (nPCR), albumin, prealbumin, insulin-like growth factor 1 (IGF-1), transferrin, and cholesterol], markers of endothelial damage and function [tissue-type plasminogen activator (tPA), thrombomodulin (TM), von Willebrand factor (vWF), and NO3 (representing NO)], markers of a coagulable state [fibrinogen and plasminogen activator inhibitor 1 (PAI-1)], markers of inflammation [tumor necrosis factor alpha (TNF alpha) and C-reactive protein (CRP)], and other endothelial injury factors [lipoprotein(a) [Lp(a)] and homocysteine]. We also performed an endothelial stimulation test consisting of right-arm venous occlusion (VO) for 10 minutes. The patients were divided into four groups according to their clinical atherosclerotic score (CAS). We studied 45 clinically stable PD patients. At baseline, statistically significant negative linear correlations were found between albumin and age (r = -0.54, p < 0.05), albumin and vWF post-VO (r = -0.54, p < 0.05), and albumin and TM (r = -0.36, p < 0.05), which are endothelial damage markers and prothrombotic factors. A positive linear correlation was seen between albumin and NO3 post-VO (r = 0.48, p < 0.05), indicating a high vasodilatation capacity. C-Reactive protein and TNF alpha showed a positive linear correlation (r = 0.5, p < 0.01). Similarly, TNF alpha showed a positive linear correlation with cardiovascular risk markers such as fibrinogen (r = 0.79, p < 0.01), PAI-1 (r = 0.44, p < 0.05), and homocysteine (r = 0.37, p < 0.05). Creatinine clearance showed a negative linear correlation with TM (r = -0.36, p < 0.05). Patients with albumin < 4 g/dL showed a lower tPA ratio, lower NO3, and a higher CRP, TNF alpha, and Lp(a) than did patients with albumin > 4 g/dL [tPA ratio: 2.1 +/- 1.56 (n = 29) vs. 2.6 +/- 2.3 (n = 16), p < 0.05; NO3: 47 +/- 27 micrograms/mL vs. 69 +/- 33 micrograms/mL, p < 0.05; CRP: 1.8 +/- 3 mg/dL vs. 1.1 +/- 1.6 mg/dL, p < 0.05; TNF alpha: 44.4 +/- 16 pg/mL vs. 36.6 +/- 21.4 pg/mL, p < 0.05; Lp(a): 55 +/- 39 mg/dL vs. 33 +/- 21 mg/dL, p < 0.05]. Patients with a worse CAS showed higher homocysteine levels and lower albumin values. Those relationships were maintained in both periods of the study. We found no relationships between dialysis dose and endothelial function markers. In conclusion, malnutrition-inflammation syndrome may contribute to endothelial dysfunction and, consequently, to prothrombotic and proatherogenic processes in PD patients.