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Background and purpose: Cytomegalovirus (CMV) infection has recently been associated with a lower multiple sclerosis (MS) susceptibility, although it remains controversial whether it has a protective role or is merely an epiphenomenon related to westernization and early‐life viral infections. We aimed to evaluate whether CMV serostatus may differ in patients with early MS as compared with patients with non‐early MS, analyzing the putative association of this virus with MS clinical course and humoral immune responses against other herpesviruses. Methods: Multicentric analysis was undertaken of 310 patients with MS (early MS, disease duration ≤5 years, n = 127) and controls (n = 155), evaluating specific humoral responses to CMV, Epstein–Barr virus and human herpesvirus‐6, as well as T‐cell and natural killer (NK)‐cell immunophenotypes. Results: Cytomegalovirus seroprevalence in early MS was lower than in non‐early MS or controls (P < 0.01), being independently associated with disease duration (odds ratio, 1.04; 95% confidence interval, 1.01–1.08, P < 0.05). CMV+ patients with MS displayed increased proportions of differentiated T‐cells (CD27−CD28−, CD57+, LILRB1+) and NKG2C+ NK‐cells, which were associated with a lower disability in early MS (P < 0.05). CMV+ patients with early MS had an age‐related decline in serum anti‐EBNA‐1 antibodies (P < 0.01), but no CMV‐related differences in anti‐human herpesvirus‐6 humoral responses. Conclusions: Low CMV seroprevalence was observed in patients with early MS. Modification of MS risk attributed to CMV might be related to the induction of differentiated T‐cell and NK‐cell subsets and/or modulation of Epstein–Barr virus‐specific immune responses at early stages of the disease. [ABSTRACT FROM AUTHOR]

Background and purpose: Different biological and radiological biomarkers predict clinical conversion to multiple sclerosis (MS) after a clinically isolated syndrome (CIS). The aim was to explore their role in predicting the outcome of patients with optic neuritis (ON), a CIS considered to have a benign prognosis. Methods: Sixty‐eight consecutive ON patients were followed prospectively. Magnetic resonance imaging (MRI) and cerebrospinal fluid studies including oligoclonal immunoglobulin G (IgG) bands (OCGBs), lipid‐specific oligoclonal IgM bands (LS‐OCMBs) and neurofilament light chain quantification were performed at disease onset. Conversion to clinically definite MS (CDMS) was monitored. Results: The mean time of follow‐up of our series was 46.4 months. Twenty‐five patients (36.7%) developed CDMS during follow‐up. Neurofilament light chain levels did not predict clinical conversion. By contrast, an abnormal MRI increased the risk of CDMS [hazard ratio (HR) 12.5, P = 0.013]. The clearest association was found in patients with more than three T2 lesions. OCGBs also predicted the onset of CDMS (HR 21.3, P = 0.003) and LS‐OCMBs were associated with a shorter time to CDMS (HR = 116.6, P < 0.001). Conclusions: Magnetic resonance imaging and OCGBs predicted conversion to CDMS after an ON episode. In addition, LS‐OCMBs identified the ON patients more likely to develop MS early. These results, applicable to the everyday clinical setting, may be of interest for therapeutic decisions. [ABSTRACT FROM AUTHOR]

Background and purpose Sperm-associated antigen 16 ( SPAG16), a sperm protein which is upregulated in reactive astrocytes in multiple sclerosis ( MS) lesions, has recently been identified as a novel autoantibody target in MS. The aim of this study was to investigate whether anti- SPAG16 antibody levels differ between MS subtypes (relapsing−remitting, RR; primary or secondary progressive, PP, SP) and whether antibody positivity is associated with clinical characteristics. Methods Plasma anti- SPAG16 antibody levels were determined by recombinant protein enzyme-linked immunosorbent assay (ELISA) in 374 MS patients (274 RRMS, 39 SPMS and 61 PPMS) and 106 healthy controls. Results Significantly elevated anti- SPAG16 antibodies were found in 22% of MS patients with 93% specificity. Anti- SPAG16 seropositivity was associated with an increased Expanded Disability Status Scale ( EDSS) in overall MS. A higher proportion of PPMS patients showed anti- SPAG16 antibody reactivity (34%) compared to RRMS (19%) and SPMS (26%), and presented with higher anti- SPAG16 antibody levels. Seropositive PPMS patients had a significantly increased progression index compared to seronegative patients. Conclusions Anti- SPAG16 antibodies are associated with an increased EDSS in overall MS, indicating that they are linked to a worse MS disease outcome. Moreover, the presence of anti- SPAG16 antibodies may be a biomarker for a more severe disease in PPMS patients, as indicated by an increased progression index. [ABSTRACT FROM AUTHOR]

Background and purpose: Chitinase 3‐like 1 (CHI3L1) and neurofilament light chain (NF‐L) are promising biomarkers of disability in multiple sclerosis (MS). However, their role in cognitive dysfunction remains elusive. Here, we aimed to correlate cerebrospinal fluid (CSF) levels of CHI3L1 and NF‐L with cognitive status in MS. Methods: Fifty one recently diagnosed patients were cognitively evaluated and CSF was collected. Levels of CHI3L1 and NF‐L were determined by ELISA. Spearman's partial correlation coefficient was performed. Results: After adjusting cognitive scores by age, anxiety and EDSS, association was detected between CHI3L1 levels and Trail Making Test A (rs = 0.348; p = 0.016) and between NF‐L levels and Word List Generation (rs = −0.324; p = 0.025). Conclusion: High levels of CSF CHI3L1 and NF‐L are associated with cognitive impairment in the early phases of MS. [ABSTRACT FROM AUTHOR]

The objective of this study was to investigate whether the presence of lipid-specific oligoclonal IgM bands (LS-OCMB) in cerebrospinal fluid (CSF) influences the response to treatment with beta-interferon in relapsing-remitting multiple sclerosis (RRMS) patients. We performed a collaborative prospective study including RRMS patients with brain MRI and LS-OCMB studies performed before starting interferon treatment. The primary endpoint was the risk of having a relapse after treatment initiation. Secondary endpoints included relapse rate, relapse-rate reduction, proportion of relapse-free patients and proportion of patients with sustained disability increase during follow-up. One-hundred and two patients were included. After a mean follow-up of 37.4 months, the risk of suffering a relapse was two-fold higher in patients with LS-OCMB (hazard ratio 2.0, 95% confidence interval 1.1-3.8). LS-OCMB+ patients showed lower reduction in relapse rate (51.8% versus 80.8%; p<0.0001), higher relapse rate in the first year (0.8 versus 0.2; p=0.001), lower proportion of relapse-free patients (25% versus 61.3%; p=0.003), and higher proportion of patients with sustained 1.0 increase in the Expanded Disability Status Score (45% versus 12.9%; p=0.0003). In conclusion, LS-OCMB can have an influence on the response to interferon treatment in RRMS patients. They could be used as a biological marker to predict high inflammatory activity after treatment. [ABSTRACT FROM AUTHOR]

Background and Objective The presence of lipid-specific immunoglobulin M bands in the cerebro-spinal fluid (CSF) predicts an aggressive course in patients with relapsing-remitting multiple sclerosis (MS) during early stages of the disease. This study examined whether it is also a predictor of long- term prognosis in MS. Methods Eighty-one patients with MS and 22 headache controls were analyzed for anti-lipid IgM reactivity in CSF samples. The correlation between the presence of lipid-specific immunoglobulin M bands in CSF and disease progression was assessed in patients with MS who had been followed longitudinally for, on average, more than 11 years. Results Lipid-specific immunoglobulin M bands were detected in the CSF of 24 of 81 patients with MS and were absent in the CSF of all headache controls. Median time to conversion to a secondary progressive course was 11 years in patients with bands and 22 years in patients without bands. Median time to an Expanded Disability Status Scale score of 4 was 14 years in patients with bands and 24 years in patients without bands. Conclusion The presence of lipid-specific immunoglobulin M bands in CSF predicts a more adverse long-term outcome in patients with MS; it may thus define a subset of patients who might benefit from aggressive treatment during the early phase of the disease. [ABSTRACT FROM AUTHOR]

Oligoclonal IgM bands (OCMB) against myelin lipids predict an aggressive multiple sclerosis (MS) course. However, the clinical significance of OCMB without lipid specificity, present in other MS patients, remains unknown. We describe here a characterization of these antibodies and study their role in MS progression. Fifty-four MS patients showing CSF-restricted OCMB were included in this study at disease onset and followed-up during 61.1 ± 2.7 months. The specificity of OCMB and the CSF B-cell profile were investigated. A second CSF IgM study was performed in a group of eight patients. Thirty-eight patients showed OCMB against myelin lipids (M+L+) and other sixteen had OCMB lacking this specificity (M+L-). The CD5+ B cell subpopulation, responsible for most persistent IgM responses, was considerably higher in M+L+ than in M+L- patients (3.3 ± 0.6% versus 0.8 ±0.2, P =0.009). In addition, M+L+ bands persisted during disease course, while M+L- disappeared during follow-up. M+L+ patients suffered more relapses (4.2 ± 0.6 versus 1.6 ± 0.3, P = 0.002) and reached higher disability (EDSS score of 2.2 ± 0.2 versus 1.2 ± 0.2, P = 0.02) than M+L- group. These data corroborate that anti-lipid OCMB associate with an aggressive MS course and show that OCMB that do not recognize myelin lipids represent a transient immune response related to a more benign disease course. [ABSTRACT FROM AUTHOR]

Lauryl gallate (antioxidant food additive E-312) prevents the formation of dimethylbenzanthracene-induced skin tumours in mice, and kills, selectively, tumoral cells on established tumours. This results in total remission, after topical application of the compound on the tumoral mass, without affecting the surrounding tissue. [ABSTRACT FROM AUTHOR]

HLA class I antigens arc thought lo be integral membrane proteins. However, soluble forms of these molecules have been detected. Our laboratory has recently shown that the predominant form of these soluble proteins present in human scrum, spleen tissue and culture supernatant of activated lymphocytes exhibits molecular weight and structure similar to classical HLA class I antigens, but lacks HLA A or B polymorphic determinants. In the present study, the secretion of such soluble proteins by lymphocytes has been further explored. Phytohaemagglutinin-stimulated normal lymphocytes secrete considerable quantities of soluble HLA (sHLA) class I proteins. This secretion seems to be a general property of lymphocytes, since activation of T as well as B cells by appropriate mitogens equally induce sHLA I secretion. Lymphocytes require RNA and protein synthesis, but not DNA synthesis, for the secretion to occur. Kinetic studies reveal that maximal sHLA 1 secretion precedes the peak of DNA synthesis by 24 h, In vitro stimulation with antigens or alloantigens also provokes sHLA I secretion. Moreover, this phenomenon has also been detected for in vivo-activated lymphocytes, as enhanced spontaneous sHLA I secretion was observed in cultures of low-density blastic B and T cells, and of blood lymphocytes obtained from normal subjects who had received a booster immunization 5 days earlier, Interferon-gamma (IPN-γ) increases the expression of membrane-bound class I antigens but does not induce any sHLA I secretion, suggesting that both molecules are under different regulatory mechanisms. Our results indicate that human lymphocytes, upon stimulation, actively secrete considerable amounts of a soluble form of these biologically relevant proteins. [ABSTRACT FROM AUTHOR]

TREM-2 is a membrane bound receptor expressed by microglia and macrophages and its engagement reduces inflammation. In this study, a soluble form of TREM 2 (sTREM-2) is identified. Cerebrospinal fluid (CSF) sTREM-2 levels were found to be higher in relapsing-remitting multiple sclerosis patients (n = 52) compared with noninflammatory neurologic diseases cases (n = 41; p = 0.004). Primary-progressive multiple sclerosis patients (n = 21) and other inflammatory neurologic diseases subjects (n = 19) also had high CSF TREM-2 levels (p < 0.001). Furthermore a subset of CSF monocytes expressed TREM-2 which was also highly expressed on myelin-laden macrophages in active demyelinating lesions. The elevated levels of sTREM-2 in the CSF of multiple sclerosis patients may inhibit the anti Inflammatory function of the membrane bound receptor. Therefore, sTREM-2 may be a possible target for future therapies. [ABSTRACT FROM AUTHOR]

The article focuses on a study which shows that patients with psoriasis have a unique profile of phenotype of peripheral blood mononuclear cells (PBMC) compared with controls. It states that presence of a low percentage of CD4+ T cells producing interferon (IFN) and of high percentages of B cells could help to identify patients not responding to classic treatments. It states that single analysis of PBMC could provide a valuable indicator to predict the need to introduce a targeted therapy.

In this work we have quantified soluble class I histocompatibility antigens (S-HLA) and β2-microglobulin (β2m) in sera of HIV+ or HIV- mothers at delivery and in cord blood sera of their newborn children. The results obtained for β2m show that cord blood sera of newborn children have higher concentrations than their mothers, implying that most of the β2m in the newborn is self- produced as described previously, s-HLA serum concentrations in the newborn children are significantly lower than in their mothers or in age-matched controls. Moreover, HIV+ mothers have significantly higher serum concentrations than HIV- mothers or an age-matched control group. These results suggest that s-HLA does not cross the placental barrier. [ABSTRACT FROM AUTHOR]

Soluble class I antigens (sHLA) are secreted by lymphocytes upon activation in vitro. The intrathecal synthesis (ITS) of these molecules has been studied in patients with the varicella-zoster virus (VZV) meningitis. In this paper we describe a sHLA index IH = (CSF sHLA/serum sHLA): (CSF albumin/serum albumin) which is expected to increase only when sHLA is synthesised within the central nervous system (CNS). The IH is elevated in the first week of meningitis, when antibody synthesis is still low, and decreases thereafter. We think IH is an index of early lymphocyte activation within the CNS. The relation of these findings with previous in vitro studies is also discussed. [ABSTRACT FROM AUTHOR]

Recent studies have begun to point out the contribution of microbiota to multiple sclerosis (MS) pathogenesis. Theiler's murine encephalomyelitis virus induced demyelinating disease (TMEV-IDD) is a model of progressive MS. Here, we first analyze the effect of intracerebral infection with TMEV on commensal microbiota and secondly, whether the early microbiota depletion influences the immune responses to TMEV on the acute phase (14 dpi) and its impact on the chronic phase (85 dpi). The intracranial inoculation of TMEV was associated with a moderate dysbiosis. The oral administration of antibiotics (ABX) of broad spectrum modified neuroimmune responses to TMEV dampening brain CD4+ and CD8+ T infiltration during the acute phase. The expression of cytokines, chemokines and VP2 capsid protein was enhanced and accompanied by clusters of activated microglia disseminated throughout the brain. Furthermore, ABX treated mice displayed lower levels of CD4+ and CD8+T cells in cervical and mesenteric lymph nodes. Increased mortality to TMEV was observed after ABX cessation at day 28pi. On the chronic phase, mice that survived after ABX withdrawal and recovered microbiota diversity showed subtle changes in brain cell infiltrates, microglia and gene expression of cytokines. Accordingly, the surviving mice of the group ABX-TMEV displayed similar disease severity than TMEV mice. [ABSTRACT FROM AUTHOR]

Objective: To validate kappa free light chain (KFLC) and lambda free light chain (LFLC) indices as a diagnostic biomarker in multiple sclerosis (MS)., Methods: We performed a multicenter study including 745 patients from 18 centers (219 controls and 526 clinically isolated syndrome (CIS)/MS patients) with a known oligoclonal IgG band (OCB) status. KFLC and LFLC were measured in paired cerebrospinal fluid (CSF) and serum samples. Gaussian mixture modeling was used to define a cut-off for KFLC and LFLC indexes., Results: The cut-off for the KFLC index was 6.6 (95% confidence interval (CI) = 5.2-138.1). The cut-off for the LFLC index was 6.9 (95% CI = 4.5-22.2). For CIS/MS patients, sensitivity of the KFLC index (0.88; 95% CI = 0.85-0.90) was higher than OCB (0.82; 95%CI = 0.79-0.85; p  < 0.001), but specificity (0.83; 95% CI = 0.78-0.88) was lower (OCB = 0.92; 95% CI = 0.89-0.96; p  < 0.001). Both sensitivity and specificity for the LFLC index were lower than OCB., Conclusion: Compared with OCB, the KFLC index is more sensitive but less specific for diagnosing CIS/MS. Lacking an elevated KFLC index is more powerful for excluding MS compared with OCB but the latter is more important for ruling in a diagnosis of CIS/MS.

Background and Purpose: Neurofilament light chain is a cytoskeletal protein of neurons. Its levels are increasingly recognized as measures of neuroaxonal damage. The aim of this study was to explore serum neurofilament light chain (sNfL) levels in multiple sclerosis (MS) patients and healthy controls during pregnancy and puerperium., Methods: This was a prospective, longitudinal, single-center study. sNfL concentration was assessed using a highly sensitive single-molecule array during pregnancy and in puerperium, in a cohort of 39 pregnant patients with relapsing multiple sclerosis (P-MS). Twenty-one healthy pregnant women (HPW) served as a control group. Eight P-MS suffered relapses during pregnancy (P-MS-R) in the first or second trimesters., Results: No differences in pregnancy and delivery data were observed between P-MS and HPW. P-MS showed higher sNfL values than HPW in the first trimester, independently of the presence (P = 0.002) or not (P = 0.02) of relapses during pregnancy. However, in the third trimester, only P-MS-R showed higher sNfL values than HPW (P = 0.001). These differences extended to the puerperium, where P-MS-R showed higher sNfL values than those with no relapses during gestation (P = 0.02)., Conclusion: These data strongly suggest that sNfL levels reflect MS activity during pregnancy. Additionally, the absence of relapses during pregnancy may have a beneficial effect on neurodegeneration during puerperium., (© 2019 EAN.)

Background and Purpose: Chitinase 3-like 1 (CHI3L1) and neurofilament light chain (NF-L) are promising biomarkers of disability in multiple sclerosis (MS). However, their role in cognitive dysfunction remains elusive. Here, we aimed to correlate cerebrospinal fluid (CSF) levels of CHI3L1 and NF-L with cognitive status in MS., Methods: Fifty one recently diagnosed patients were cognitively evaluated and CSF was collected. Levels of CHI3L1 and NF-L were determined by ELISA. Spearman's partial correlation coefficient was performed., Results: After adjusting cognitive scores by age, anxiety and EDSS, association was detected between CHI3L1 levels and Trail Making Test A (r s = 0.348; p = 0.016) and between NF-L levels and Word List Generation (r s = -0.324; p = 0.025)., Conclusion: High levels of CSF CHI3L1 and NF-L are associated with cognitive impairment in the early phases of MS., (© 2018 EAN.)

Background: This study aims to compare the efficiency of four oral fluid collection methods (Salivette, FTA Card, spitting and DNA-Sal) to detect HBV DNA by qualitative PCR., Materials and Methods: Seventy-four individuals (32 HBV reactive and 42 with no HBV markers) donated serum and oral fluid. In-house qualitative PCR to detect HBV was used for both samples and commercial quantitative PCR for serum., Results: HBV DNA was detected in all serum samples from HBV-infected individuals, and it was not detected in control group. HBV DNA from HBV group was detected in 17 samples collected with Salivette device, 16 samples collected by FTA Card device, 16 samples collected from spitting and 13 samples collected by DNA-Sal device. Samples that corresponded to a higher viral load in their paired serum sample could be detected using all oral fluid collection methods, but Salivette collection device yielded the largest numbers of positive samples and had a wide range of viral load that was detected., Conclusion: It was possible to detect HBV DNA using all devices tested, but higher number of positive samples was observed when samples were collected using Salivette device, which shows high concordance to viral load observed in the paired serum samples., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. All rights reserved.)

Renowned national specialists in multiple sclerosis (MS) met, for the eighth year in a row, to give details of the latest novelties presented at the last ECTRIMS Congress 2015, which are included in this review. One of the highlights at this Congress was the new classification of the phenotypes of MS. Both the diagnostic criteria of the neuromyelitis optica spectrum and the problems involved in the differential diagnosis derived from the lack of definition of the radiological spectrum were reviewed. The microbiota comes to the fore as a possible factor determining the disease, together with extrinsic factors such as tobacco, salt ingestion or vitamin D deficiency. Advances made in immunomodulation are driving the progress being made in the treatment of MS. Ocrelizumab is the first treatment with positive results in the primarily progressive forms and tocilizumab, a drug product for rheumatoid arthritis, stands out as a potential candidate for the treatment of neuromyelitis optica. Certain antibiotics and vitamins could also play a role in the treatment of MS. In this edition of the Congress special attention was paid to personalised therapy. To date, 11 drugs have been approved for use in Europe. There is a need for therapeutic algorithms that help us to choose the best treatment for each patient. Likewise, we need to be able to identify, in the early stages of the disease, the risk of developing disability, so as to be able to design therapeutic strategies. To do so, molecular biomarkers and other predictive tools are required. The problems that still exist in software technology in magnetic resonance hinder its application in daily clinical practice.

We present guidelines from the Immunochemistry group of the Spanish Society for Immunology that are designed to provide a practical tool for the diagnosis and follow-up of monoclonal gammopathies. We review the clinical and analytical features of various monoclonal gammopathies, international consensus guidelines and techniques used to detect and follow-up monoclonal components., (Copyright © 2015 Elsevier España, S.L.U. y Sociedad Española de Medicina Interna (SEMI). All rights reserved.)

Background and Objective: We explored which clinical and biochemical variables predict conversion from clinically isolated syndrome (CIS) to clinically definite multiple sclerosis (CDMS) in a large international cohort., Methods: Thirty-three centres provided serum samples from 1047 CIS cases with at least two years' follow-up. Age, sex, clinical presentation, T2-hyperintense lesions, cerebrospinal fluid (CSF) oligoclonal bands (OCBs), CSF IgG index, CSF cell count, serum 25-hydroxyvitamin D3 (25-OH-D), cotinine and IgG titres against Epstein-Barr nuclear antigen 1 (EBNA-1) and cytomegalovirus were tested for association with risk of CDMS., Results: At median follow-up of 4.31 years, 623 CIS cases converted to CDMS. Predictors of conversion in multivariable analyses were OCB (HR = 2.18, 95% CI = 1.71-2.77, p < 0.001), number of T2 lesions (two to nine lesions vs 0/1 lesions: HR = 1.97, 95% CI = 1.52-2.55, p < 0.001; >9 lesions vs 0/1 lesions: HR = 2.74, 95% CI = 2.04-3.68, p < 0.001) and age at CIS (HR per year inversely increase = 0.98, 95% CI = 0.98-0.99, p < 0.001). Lower 25-OH-D levels were associated with CDMS in univariable analysis, but this was attenuated in the multivariable model. OCB positivity was associated with higher EBNA-1 IgG titres., Conclusions: We validated MRI lesion load, OCB and age at CIS as the strongest independent predictors of conversion to CDMS in this multicentre setting. A role for vitamin D is suggested but requires further investigation., (© The Author(s), 2015.)

Background: The presence of oligoclonal IgM bands (OCMB) in cerebrospinal fluid (CSF) is an unfavourable prognostic marker in multiple sclerosis. There is no commercial test to investigate OCMB status. However, a sensitive and specific isoelectrofocusing (IEF) and western blot method was described. We aimed to study the inter-centre reproducibility of this technique, a necessary condition for a reliable test to be incorporated into clinical practice., Methods: The presence of OCMB was analysed by IEF and western blot with prior reduction of pentameric IgM. We assayed the reproducibility of this test in a blinded multicentre study performed in 13 university hospitals. Paired-CSF and serum samples from 52 neurological patients were assayed at every centre., Results: Global analysis rendered a concordance of 89.8% with a kappa value of 0.71., Conclusion: These data indicate that OCMB detection by means of IEF and western blot with IgM reduction shows a good interlaboratory reproducibility and thus can be used in daily clinical setting., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Background: Enzyme immunoassays (EIA) designed to detect hepatitis C virus (HCV) core antigen and anti-HCV antibodies (HCV AgAb) simultaneously can improve the early detection of HCV infection when molecular diagnostic methods are not widely available., Objectives: To evaluate the suitability of dried blood spot (DBS) samples for detecting HCV AgAb using commercial EIAs., Study Design: Paired serum and DBS samples were assayed using two commercial EIAs for HCV AgAb (Monolisa™ HCV AgAb ULTRA and Murex HCV AgAb). Manufacturer's recommendations were followed for sera while sample volume, incubation time and cut-off (CO) determination were evaluated for the DBS samples. The values of sensitivity, specificity, inter-rater agreement, detection limit, assay precision and stability of DBS samples at different conditions (22-26°C, 2-8°C and -20°C) were determined., Results: It was necessary to increase the DBS sample volume fourfold compared to the sera samples to approximate the DBS Optical Density (OD) values to the sera OD values. Using ROC curve to recalculate CO values for the DBS samples, sensitivity was 97.5% for both EIAs, while the specificity was 99.71% for Monolisa™ HCV AgAb ULTRA and 95.95% for Murex HCV AgAb. Accurate testing results were obtained with DBS samples for 60 days at all conditions evaluated; storage at -20°C resulted in low OD variation. Both EIAs demonstrated the same limit of detection among DBS samples [estimated viral load of 3.1 International Units per millilitre (IU/mL)] and low OD value variability in repetitivity and reproducibility studies., Conclusion: DBS samples can be used for the detection of HCV AgAb by EIA as they present comparable performance characteristics and excellent stability among various storage conditions., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Background: Antibody responses to standard regimens of hepatitis B (HBV) vaccination are lower in HIV-infected subjects and the best hepatitis B vaccine schedule in this population is not known., Objective: To assess the immunogenicity and to evaluate predictors of serologic response of a modified regimen of a HBV recombinant vaccine in a cohort of HIV-infected subjects., Methods: HIV-infected subjects received 4 doses (40 μg) of a recombinant HBV vaccine at 0, 1, 2 and 6 months. Demographic information as well as CD4 cell count and plasma viral load were assessed at baseline. Protective and strong responses were defined as an anti-HBs titer ≥10 mIU/mL and ≥100 mIU/mL, respectively and were evaluated one month after the third and the fourth doses., Results: 163 HIV-infected individuals were evaluated 67 (40%) were male and median age was 37 years. Median CD4 cell count was 385 cells/mm(3) and 113 (70%) had undetectable HIV-1 viral load. Protective antibody response was observed in 83 and 91% and a strong antibody response was observed in 62 and 80% of the subjects after 3 and 4 doses, respectively. In a multivariate logistic model undetectable HIV-1 viral load and higher CD4 cell counts were independent predictors of a strong antibody response after 4 doses. Patients with undetectable HIV viral load were almost 3 times more likely to have anti-HBs titers above 100 mIU/mL than those with detectable viral load., Conclusions: A 4-double-dose regimen of a recombinant HBV vaccine increased response rates and determined higher antibody titers which may translate in prolonged protection against HBV. Inclusion of a fourth dose of HBV vaccine for HIV-infected subjects should be considered in the public health setting., (Copyright © 2012 Elsevier Ltd. All rights reserved.)