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Objectives Emerging evidence demonstrates that aPS-PT associate with thrombotic events. Genetic predisposition, including HLA-DRB1 alleles, is known to contribute to the occurrence of conventional aPL [anti-β2glycoprotein-I (anti-β2GPI) and aCL]. We investigated associations between aPS-PT and HLA-DRB1* alleles and thrombosis in SLE. Conventional aPL were included for comparison. Methods We included 341 consecutive SLE patients, with information on general cardiovascular risk factors, including blood lipids, LA and thrombotic events. aPS/PT, anti-β2GPI and aCL of IgA/G/M isotypes and LA were quantified. Results aPS/PT antibodies associated positively with HLA-DRB1*13 [odds ratio (OR) 2.7, P = 0.002], whereas anti-β2GPI and aCL antibodies associated primarily with HLA-DRB1*04 (OR 2.5, P = 0.0005). These associations remained after adjustment for age, gender and other HLA-DRB1* alleles. HLA-DRB1*13, but not DRB1*04, remained as an independent risk factor for thrombosis and APS after adjustment for aPL and cardiovascular risk factors. The association between DRB1*13 and thrombosis was mediated by aPS-PT positivity. HLA-DRB1*03, on the other hand, associated negatively with thrombotic events as well as all aPL using both uni- and multivariate analyses. HLA-DRB1*03 had a thrombo-protective effect in aPL-positive patients. Additionally, HLA-DRB1*03 was associated with a favourable lipid profile regarding high-density lipoprotein and triglycerides. Conclusions HLA-DRB1*13 confers risk for both aPS-PT and thrombotic events in lupus. The association between HLA-DRB1*13 and thrombosis is largely, but not totally, mediated through aPS-PT. HLA-DRB1*03 was negatively associated with aPL and positively with favourable lipid levels. Thus, HLA-DRB1*03 seems to identify a subgroup of SLE patients with reduced vascular risk.

Background Low levels of total C4b-binding protein (C4BPt), a circulating inhibitor of the classical/lectin complement pathways, were observed in patients with antiphospholipid antibodies (aPLs) and during warfarin treatment. Objectives To investigate the associations between aPL and C4BPt in patients with persistently positive (++) aPL, with/without clinical manifestations and systemic lupus erythematosus (SLE), and in controls. Furthermore, we explored the impact of anticoagulation on C4BPt and in relation to complement activation. Methods In a cross-sectional design we investigated defined subgroups: primary (p) antiphospholipid syndrome (APS, N = 67), aPL++ individuals without clinical manifestations (aPL carriers, N = 15), SLE-aPL++ (N = 118, among them, secondary [s] APS, N = 56), aPL negative (−) SLE (SLE-aPL−, N = 291), and 322 controls. Clinical characteristics, including treatment, were tabulated. C4BPt was determined with a magnetic bead method. Complement proteins (C1q, C2, C3, C4, C3a, C3dg, sC5b-9, factor I [FI]) were measured. A mediation analysis was performed to decompose the total effect of aPL++ on C4BPt into the direct and indirect effects of aPL++ through warfarin. Results Overall, C4BPt is 20% decreased in aPL++ patients, regardless of SLE, APS, clinical manifestations, and aPL profile. C4BPt levels associate positively with complement proteins C1q, C2, C3, and C4, and negatively with complement activation product C3dg. In the SLE group, warfarin treatment contributes to approximately half of the C4BPt reduction (9%) Conclusion Both aPLs and warfarin are associated with C4BPt reduction. Complement activation in aPL++ patients may partly be explained by impaired inhibition through depressed C4BPt levels. Further studies are needed to understand the clinical implications.

Objectives Antiphosphatidylserine/prothrombin complex antibodies (aPS/PT) are risk factors for thrombosis, yet further validation of their clinical relevance in different ethnic groups is required. We investigated the performance of aPS/PT of IgA/G/M isotypes among Sudanese and Swedish systemic lupus erythematosus (SLE) patients. Methods Consecutive SLE patients/matched controls from Sudan (n = 91/102) and Sweden (n = 332/163) were included. All patients fulfilled the 1982 ACR SLE classification criteria. IgA/G/M of aPS/PT, anti-cardiolipin and anti-β2glycoprotein I (anti-β2GPI) were tested in both cohorts, and lupus anticoagulant (LA) also in the Swedish cohort. Clinical antiphospholipid syndrome-related events and atherosclerosis, measured as carotid plaques were assessed for associations. Univariate and multivariate analyses adjusting for cardiovascular risk factors were performed. Results Sudanese SLE patients had higher levels of IgM aPS/PT, but using national cut-offs, the frequency of positivity was similar to Swedish patients for all isotypes. Among Swedish patients, all isotypes of aPS/PT associated with venous thromboembolism (VTE), while only IgA aPS/PT associated with arterial thrombosis (AT). aPS/PT antibodies associated strongly with LA and they were, independently, the best predictor for VTE. Double positivity for aPS/PT and anti-β2GPI associated with higher VTE risk than the conventional triple positivity. Carotid plaques did not associate with any antiphospholipid antibody. Conclusions IgA aPS/PT associated with AT, and the association of IgG/M aPS/PT with VTE outperforms LA and criteria antiphospholipid antibodies in Swedish SLE patients. Furthermore, double positivity for aPS/PT and anti-β2GPI performed better than conventional triple positivity. Future studies need to address if aPS/PT can replace LA, as this would simplify clinical procedures.

Objective Complement components, including C4d, can be found on activated platelets, a process associated with vascular disease in systemic lupus erythematosus (SLE). We investigated whether platelet C4d (PC4d) adds additional value to traditional and known lupus-associated risk factors when identifying SLE patients with vascular disease. Method This cross-sectional study, included 308 well-characterized SLE patients and 308 matched general population controls. PC4d deposition was analyzed using flow cytometry. Values >95% of controls were considered as PC4d positive (+). Antiphospholipid antibodies (aPL) were determined by Luminex, and the lupus anticoagulant (LA) test was performed by the DRVVT test. History of vascular disease (composite and as separate outcomes) was defined at inclusion. Results SLE patients had increased PC4d deposition as compared to population controls (50% versus 5%, p Conclusions PC4d+ is associated with vascular events in SLE, independently of traditional and SLE-associated risk factors. Concurrent presence of PC4d and LA seem to interact to further increase the odds for vascular events. Prospective studies should examine whether the aPL/PC4d combination can improve prediction of vascular events in SLE and/or APS.

Thrombosis and complement activation are pathogenic features of antiphospholipid syndrome (APS). Their molecular link is Plasma carboxypeptidase-B, also known as thrombin activatable fibrinolysis inhibitor (TAFIa), which plays a dual role: anti-fibrinolytic, by cleaving carboxyl-terminal lysine residues from partially degraded fibrin, and anti-inflammatory, by downregulating complement anaphylatoxins C3a and C5a.To investigate the levels of TAFI (proenzyme) and TAFIa (active enzyme) in relation to complement activation, fibrin clot permeability and fibrinolytic function in clinical and immunological subsets of 52 APS patients and 15 controls.TAFI (p0.001), TAFIa (p0.05) and complement factor C5a (p0.001) were increased, while fibrin permeability (p0.01) was decreased and clot lysis time (CLT) was prolonged (p0.05) in APS patients compared to controls. Furthermore, TAFIa was increased (p0.01) in samples from APS patients affected by arterial thrombosis compared to other APS-phenotypes. Positive associations were found between TAFI and age, fibrinogen and C5a, and between TAFIa and age, fibrinogen and thrombomodulin.TAFI and TAFIa levels were increased in patients with APS as a potential response to complement activation. Interestingly, TAFI activation was associated with arterial thrombotic APS manifestations. Thus, TAFIa may be considered a novel biomarker for arterial thrombosis in APS.

ObjectiveComplement components, including C4d, can be found on activated platelets, a process associated with vascular disease in SLE. We investigated whether platelet C4d (PC4d) adds additional value to traditional and known lupus-associated risk factors when identifying SLE patients with vascular disease.MethodsThis cross-sectional study included 308 well-characterized SLE patients and 308 matched general population controls. PC4d deposition was analysed using flow cytometry. Values >95% of controls were considered as PC4d positive (+). aPL were determined by Luminex, and the LA test was performed by DRVVT. History of vascular disease (composite and as separate outcomes) was defined at inclusion.ResultsSLE patients had increased PC4d deposition as compared with population controls (50 vs 5%, P ConclusionPC4d+ is associated with vascular events in SLE, independently of traditional and SLE-associated risk factors. Concurrent presence of PC4d and LA seem to interact to further increase the odds for vascular events. Prospective studies should examine whether the aPL/PC4d combination can improve prediction of vascular events in SLE and/or APS.

Background Previous studies and own clinical observations of patients with systemic lupus erythematosus (SLE) suggest that SLE harbors distinct immunophenotypes. This heterogeneity might result in differences in response to treatment in different subgroups and obstruct clinical trials. Our aim was to understand how SLE subgroups may differ regarding underlying pathophysiology and characteristic biomarkers. Methods In a cross-sectional study, including 378 well-characterized SLE patients and 316 individually matched population controls, we defined subgroups based on the patients’ autoantibody profile at inclusion. We selected a core of an antiphospholipid syndrome-like SLE (aPL+ group; positive in the lupus anticoagulant (LA) test and negative for all three of SSA (Ro52 and Ro60) and SSB antibodies) and a Sjögren’s syndrome-like SLE (SSA/SSB+ group; positive for all three of SSA (Ro52 and Ro60) and SSB antibodies but negative in the LA test). We applied affinity-based proteomics, targeting 281 proteins, together with well-established clinical biomarkers and complementary immunoassays to explore the difference between the two predefined SLE subgroups. Results The aPL+ group comprised 66 and the SSA/SSB+ group 63 patients. The protein with the highest prediction power (receiver operating characteristic (ROC) area under the curve = 0.89) for separating the aPL+ and SSA/SSB+ SLE subgroups was integrin beta-1 (ITGB1), with higher levels present in the SSA/SSB+ subgroup. Proteins with the lowest p values comparing the two SLE subgroups were ITGB1, SLC13A3, and CERS5. These three proteins, rheumatoid factor, and immunoglobulin G (IgG) were all increased in the SSA/SSB+ subgroup. This subgroup was also characterized by a possible activation of the interferon system as measured by high KRT7, TYK2, and ETV7 in plasma. In the aPL+ subgroup, complement activation was more pronounced together with several biomarkers associated with systemic inflammation (fibrinogen, α-1 antitrypsin, neutrophils, and triglycerides). Conclusions Our observations indicate underlying pathogenic differences between the SSA/SSB+ and the aPL+ SLE subgroups, suggesting that the SSA/SSB+ subgroup may benefit from IFN-blocking therapies while the aPL+ subgroup is more likely to have an effect from drugs targeting the complement system. Stratifying SLE patients based on an autoantibody profile could be a way forward to understand underlying pathophysiology and to improve selection of patients for clinical trials of targeted treatments. Electronic supplementary material The online version of this article (10.1186/s13075-019-1836-8) contains supplementary material, which is available to authorized users.

Systemic Lupus Erythematosus (SLE) is a heterogeneous autoimmune disease, which currently lacks specific diagnostic biomarkers. The diversity within the patients obstructs clinical trials but may also reflect differences in underlying pathogenesis. Our objective was to obtain protein profiles to identify potential general biomarkers of SLE and to determine molecular subgroups within SLE for patient stratification. Plasma samples from a cross-sectional study of well-characterized SLE patients (n = 379) and matched population controls (n = 316) were analyzed by antibody suspension bead array targeting 281 proteins. To investigate the differences between SLE and controls, Mann-Whitney U-test with Bonferroni correction, generalized linear modeling and receiver operating characteristics (ROC) analysis were performed. K-means clustering was used to identify molecular SLE subgroups. We identified Interferon regulating factor 5 (IRF5), solute carrier family 22 member 2 (SLC22A2) and S100 calcium binding protein A12 (S100A12) as the three proteins with the largest fold change between SLE patients and controls (SLE/Control = 1.4, 1.4, and 1.2 respectively). The lowest p-values comparing SLE patients and controls were obtained for S100A12, Matrix metalloproteinase-1 (MMP1) and SLC22A2 (padjusted = 3 × 10-9, 3 × 10-6, and 5 × 10-6 respectively). In a set of 15 potential biomarkers differentiating SLE patients and controls, two of the proteins were transcription factors, i.e., IRF5 and SAM pointed domain containing ETS transcription factor (SPDEF). IRF5 was up-regulated while SPDEF was found to be down-regulated in SLE patients. Unsupervised clustering of all investigated proteins identified three molecular subgroups among SLE patients, characterized by (1) high levels of rheumatoid factor-IgM, (2) low IRF5, and (3) high IRF5. IRF5 expressing microparticles were analyzed by flow cytometry in a subset of patients to confirm the presence of IRF5 in plasma and detection of extracellular IRF5 was further confirmed by immunoprecipitation-mass spectrometry (IP-MS). Interestingly IRF5, a known genetic risk factor for SLE, was detected extracellularly and suggested by unsupervised clustering analysis to differentiate between SLE subgroups. Our results imply a set of circulating molecules as markers of possible pathogenic importance in SLE. We believe that these findings could be of relevance for understanding the pathogenesis and diversity of SLE, as well as for selection of patients in clinical trials.

Systemic lupus erythematosus (SLE, OMIM 152700) is a systemic autoimmune disease with a complex etiology. The mode of inheritance of the genetic risk beyond familial SLE cases is currently unknown. Additionally, the contribution of heterozygous variants in genes known to cause monogenic SLE is not fully understood. Whole-genome sequencing of DNA samples from 71 Swedish patients with SLE and their healthy biological parents was performed to investigate the general genetic risk of SLE using known SLE GWAS risk loci identified using the ImmunoChip, variants in genes associated to monogenic SLE, and the mode of inheritance of SLE risk alleles in these families. A random forest model for predicting genetic risk for SLE showed that the SLE risk variants were mainly inherited from one of the parents. In the 71 patients, we detected a significant enrichment of ultra-rare (0.1%) missense and nonsense mutations in 22 genes known to cause monogenic forms of SLE. We identified one previously reported homozygous nonsense mutation in the C1QC (Complement C1q C Chain) gene, which explains the immunodeficiency and severe SLE phenotype of that patient. We also identified seven ultra-rare, coding heterozygous variants in five genes (C1S, DNASE1L3, DNASE1, IFIH1, and RNASEH2A) involved in monogenic SLE. Our findings indicate a complex contribution to the overall genetic risk of SLE by rare variants in genes associated with monogenic forms of SLE. The rare variants were inherited from the other parent than the one who passed on the more common risk variants leading to an increased genetic burden for SLE in the child. Higher frequency SLE risk variants are mostly passed from one of the parents to the offspring affected with SLE. In contrast, the other parent, in seven cases, contributed heterozygous rare variants in genes associated with monogenic forms of SLE, suggesting a larger impact of rare variants in SLE than hitherto reported. Funding Agencies|Knut and Alice Wallenberg Foundation; Swedish Research Council for Medicine and Health [D0283001, 2017-02000]; Swedish Rheumatism Association; King Gustaf Vs 80-year Foundation; Swedish Society of Medicine; Swedish Research Council for Infrastructures (VR-RFI)

Background:Complement plays a role in the Antiphospholipid Syndrome (APS). C4b Binding Protein (C4BP) is a complement inhibitor with anticoagulant function (1). It belongs to the same protein family as β2GPI, the main antigen in APS. Its main isoform is bound to protein S in the circulation. Levels of both protein S and C4BP are known to be reduced by warfarin treatment (2) as well as by aPL, directly and indirectly.Objectives:To investigate the levels of C4BP in primary (p) and secondary (s) APS, also considering warfarin treatment.Methods:The total amount of C4BP (C4BPt) was measured by using magnetic carboxylated microspheres which were coupled with a monoclonal antibody against the α-chain of human-C4BP to capture the antigen. To detect C4BPt the same antibody was used, biotinylated. The binding of biotinylated antibodies was detected by streptavidin-phycoerythrin and data were collected using a MAGPIX Multiplex Reader. Using independent t-test, we compared C4BP in 118 SLE patients with repeated positivity for Antiphospholipid antibodies (aPL) (39/118 on warfarin), 291 aPL negative SLE patients (16/291 on warfarin), 67 pAPS (33/67 on warfarin), and 322 controls (none on warfarin). We then performed an interaction and a mediation analysis (3) in the SLE group to study the impact of warfarin on C4BP levels: since warfarin is mostly prescribed to aPL+ patients, it is considered a mediator in the reducing effect of aPL on C4BP. Therefore we compared individuals exposed and non-exposed to the presence of aPL with or without the mediator warfarin and calculated the percentage of reduction in C4BP that could be attributed to aPL or warfarin.Results:Overall C4BP is 20% reduced in aPL+ patients (fig 1), independently of SLE, past thrombotic events and nephritis. Warfarin treated patients have lower levels of C4BP (fig 2). According to mediation analysis 11% of C4BP reduction is due to aPL and 9% to warfarin.Figure 1.C4BP in different subgroups (67 pAPS, 118 SLEaPL+, 291 SLEaPL-, 322 controls)Figure 2.C4BP in 67 pAPS patients, 33/67 on warfarinConclusion:Both aPL and warfarin decrease levels of C4BP, a complement and coagulation regulator. Reduction of this complement inhibitor could contribute to complement activation and thrombosis in APS. Our results raise new questions regarding the effects of warfarin treatment on complement and coagulation in APS.References:[1]Dahlbäck B. C4b-binding protein: a forgotten factor in thrombosis and hemostasis. Seminars in thrombosis and hemostasis 2011; 37(4): 355.[2]Zöller B, García de Frutos P, Dahlbäck B. Evaluation of the relationship between protein S and C4b-binding protein isoforms in hereditary protein S deficiency demonstrating type I and type III deficiencies to be phenotypic variants of the same genetic disease. Blood 1995; 85(12): 3524.[3]Vanderweele TJ, Vansteelandt S. Conceptual issues concerning mediation, interventions and composition. Statistics and Its Interface 2009; 2(4): 457-68.Disclaimer:AV is employed at the Swedish Medical Products Agency, the views expressed in this paper are the personal views of the authors and not necessarily the views of the Governement AgencyAcknowledgments:Thanks to the Biostatistics Core Facility, Karolinska UniversityDisclosure of Interests:None declared

Background:Cardiovascular disease is a serious complication in patients with dysglycaemia, defined as either type 2 diabetes or impaired glucose tolerance. Research focusing on the identification of potential markers for atherothrombotic disease in these subjects is warranted. The antiphospholipid syndrome is a common acquired prothrombotic condition, defined by a combination of thrombotic events and/or obstetric morbidity and positivity of specific antiphospholipid antibodies. Available information on antiphospholipid antibodies in dysglycaemia is scarce.Objective:This study investigates the association between antiphospholipid antibodies and dysglycaemia.Patients/Methods:The PAROKRANK (periodontitis and its relation to coronary artery disease) study included 805 patients, investigated 6–10 weeks after a first myocardial infarction, and 805 matched controls. Participants without known diabetes (91%) underwent an oral glucose tolerance test. Associations between antiphospholipid antibodies (anti-cardiolipin and anti-β2 glycoprotein-I IgG, IgM and IgA) and dysglycaemia were analysed.Results:In total, 137 (9%) subjects had previously known type 2 diabetes and 371 (23%) newly diagnosed dysglycaemia. Compared with the normoglycaemic participants, those with dysglycaemia had a higher proportion with first myocardial infarction (61% vs 45%, p Conclusions:This study reports an association between antiphospholipid antibody IgG positivity and dysglycaemia. Further studies are needed to verify these findings and to investigate if antithrombotic therapy reduces vascular complications in antiphospholipid antibody positive subjects with dysglycaemia.

Background: Antiphospholipid syndrome (APS) is defined by arterial, venous, or microvascular thrombosis or obstetric morbidity together with confirmed positive test results, at least 12 weeks apart ...

Objectives IgG- and IgM-class anti-cardiolipin antibodies (aCL) and lupus anticoagulant (LA) are included in the 1997 update of the American College of Rheumatology (ACR-97) systemic lupus erythematosus (SLE) classification criteria. Despite limited evidence, IgA-aCL and IgA anti-β2-glycoprotein-I (anti-β2GPI) were included among the 2012 Systemic Lupus International Collaborating Clinics classification criteria. The present study was undertaken to evaluate IgG-/IgA-/IgM-aCL and anti-β2GPI occurrence in relation to disease phenotype, smoking habits, pharmacotherapy, APS-related events, and organ damage among Swedish SLE patients. Methods 526 SLE patients meeting ACR-97 were included. Blood donors and patients with rheumatoid arthritis or primary Sjogren’s syndrome served as controls. Serum anti-phospholipid antibodies (aPL) were analysed by enzyme-immunoassays. Results 76 (14%) SLE cases fulfilled the Sydney APS-criteria, and at least 1 aCL/anti-β2GPI isotype (IgG/IgA/IgM) occurred in 138 SLE patients (26%). 44 (8%) of the SLE cases had IgA-aCL, of whom 20 (4%) lacked IgG-/IgM-aCL. 74 (14%) tested positive for IgA anti-β2GPI, 34 (6%) being seronegative regarding IgG/IgM anti-β2GPI. 6 (1%) had manifestations compatible with APS and were seropositive regarding IgA-aCL and/or IgA anti-β2GPI in absence of IgG/IgM-aPL and LA. Positive LA- and IgG-aPL tests associated with most APS-related events and organ damage. Exclusive IgA anti-β2GPI occurrence associated inversely with Caucasian ethnicity and photosensitivity. Nephritis, smoking, LA-positivity and statin/corticosteroid-medication associated strongly with organ damage, whereas ongoing hydroxychloroquinemedication was protective. Conclusions IgA-aPL is not uncommon in SLE (16%). Exclusive IgA anti-β2GPI±IgA aCL associated with non-Caucasian ethnicity. IgA-aPL analysis may be of additional value among clinically suspected APS-patients testing negative for other isotypes of aPL and LA.

Immunoglobulin (Ig) G- and IgM-class anti-cardiolipin antibodies (aCL) and lupus anti-coagulant (LA) are included in the 1997 update of the American College of Rheumatology (ACR-97) systemic lupus erythematosus (SLE) criteria. Despite limited evidence, IgA-aCL and IgA anti-(2)-glycoprotein-I (anti-(2)GPI) were included in the 2012 Systemic Lupus International Collaborating Clinics criteria. The present study aimed to evaluate IgG-/IgA-/IgM-aCL and anti-(2)GPI occurrence in relation to disease phenotype, smoking habits, pharmacotherapy, anti-phospholipid syndrome (APS) and organ damage among 526 Swedish SLE patients meeting ACR-97. Patients with rheumatoid arthritis (n=100), primary Sjogrens syndrome (n=50) and blood donors (n=507) served as controls. Anti-phospholipid antibodies (aPL) were analysed by fluoroenzyme-immunoassays detecting aCL/anti-(2)GPI. Seventy-six (14%) SLE cases fulfilled the Sydney APS-criteria, and 1 aCL/anti-(2)GPI isotype (IgG/IgA/IgM) occurred in 138 SLE patients (26%). Forty-five (9%) of the SLE cases had IgA-aCL, 20 of whom (4%) lacked IgG-/IgM-aCL. Seventy-four (14%) tested positive for IgA anti-(2)GPI, 34 (6%) being seronegative regarding IgG/IgM anti-(2)GPI. Six (1%) had APS manifestations but were seropositive regarding IgA-aCL and/or IgA anti-(2)GPI in the absence of IgG/IgM-aPL and LA. Positive LA and IgG-aPL tests were associated with most APS-related events and organ damage. Exclusive IgA anti-(2)GPI occurrence associated inversely with Caucasian ethnicity [odds ratio (OR)=021, 95% confidence interval (CI)=006-072) and photosensitivity (OR=019, 95% CI=005-072). Nephritis, smoking, LA-positivity and statin/corticosteroid-medication associated strongly with organ damage, whereas hydroxychloroquine-medication was protective. In conclusion, IgA-aPL is not rare in SLE (16%) and IgA-aPL analysis may have additional value among SLE cases with suspected APS testing negative for other isotypes of aPL and LA. Funding Agencies|Swedish Society for Medical Research; Swedish Rheumatism Association; Swedish Society of Medicine; King Gustaf Vs 80-year foundation; King Gustaf V and Queen Victorias Freemasons foundation; Swedish Heart-Lung Foundation; Swedish Research Council; County Council of Stockholm; County Council of Uppsala; County Council of Ostergotland

Natural IgM autoantibodies have been proposed to convey protection from autoimmune pathogenesis. Herein, we investigated the IgM responses in 396 systemic lupus erythematosus (SLE) patients, divided into subgroups based on distinct autoantibody profiles. Depressed IgM levels were more common in SLE than in matched population controls. Strikingly, an autoreactivity profile defined by IgG anti-Ro/La was associated with reduced levels of specific natural IgM anti-phosphorylcholine (PC) antigens and anti-malondialdehyde (MDA) modified-protein, as well total IgM, while no differences were detected in SLE patients with an autoreactivity profile defined by anti-cardiolipin/Beta2glycoprotein-I. We also observed an association of reduced IgM levels with the HLA-DRB1*03 allelic variant amongst SLE patients and controls. Associations of low IgM anti-PC with cardiovascular disease were primarily found in patients without antiphospholipid antibodies. These studies further highlight the clinical relevance of depressed IgM. Our results suggest that low IgM levels in SLE patients reflect immunological and genetic differences between SLE subgroups., Comment: Clin Immunol. 2017 Sep 15

The introduction of antiretroviral therapy (ART) has substantially modified the clinical history and epidemiology of HIV infection with an important decline in infective causes of death and an increase in non-infective comorbidities particularly in cardiovascular complications. HIV infection has been related to an increased cardiovascular risk due to the presence of three factors: classic cardiovascular risk factors (shared with the general population), HIV infection itself (indirectly due to the inflammation and directly due to viral molecule) and ART-related chronic metabolic alterations. We describe a peculiar case of metabolic alteration in an HIV infected patient on ART with particular attention to the diagnosis and therapeutic aspects. Giving the higher cardiovascular risk of this specific population it is advisable that the clinician performs a frequent re-assessment of risk factors and cardiovascular organ damage. An early detection of metabolic alteration must lead to an aggressive specific therapy; this must be done by taking care of the HIV-infected subject fragility and the interactions with ART.

This case report concerns an elderly woman referred with a 6-month history of rising and falling fever in the range 38-40°C. She was examined repeatedly by her family doctor and given various antibiotic treatments before being hospitalized in our geriatric unit. Laboratory tests and microbiological studies led to a diagnosis of chronic Q fever, a zoonosis caused by Coxiella burnetii, a Gram-negative obligate intracellular coccobacillus; humans usually become infected by inhaling infectious airborne particles. The diagnosis of Q fever relies on serology with enzyme immunoassay (EIA). The main feature of Q fever is its clinical polymorphism: clinical signs may be aspecific and, in chronic cases, patients often do not recall having had the acute infection. As the most frequent and severe manifestation of Q fever is endocarditis, severe consequences may ensue. In our patient, broad-spectrum antibiotics were given before the serology results were available and rapid clinical improvement was achieved. This unusual disease should therefore also be considered in differential diagnosis of fever in the elderly, and age should not be considered as a contraindication for not performing all studies, because timely and adequate treatment is important partly to preserve elderly patients' self-sufficiency and to prevent them from becoming bedridden.

Blood pressure (BP) measurement in clinical assessment by means of a mercury sphygmomanometer (MS) has numerous drawbacks. It has been proposed that non-invasive, 24-hr ambulatory blood pressure monitoring (NIABPM) should provide more appropriate BP values for both the diagnosis of hypertension and for its subsequent monitoring during treatment. The aim of the present study was to investigate, in 100 ambulatory and 250 hospitalized elderly subjects, the prevalence of white coat hypertension (WCH) and masked hypertension (MH) in a cohort of older subjects, by using both clinical readings (MS) and NIABPM. The results of our analyses indicate that a higher prevalence of old-old subjects regarded as normotensive at anamnesis or with normal BP values at MS are true hypertensive (50% of ambulatory patients and 17.1% of hospitalized patients) or masked hypertensive (10.3% of ambulatory patients and 28.6% of hospitalized patients), and consequently at higher risk of cardiovascular morbidity and mortality.