A study of antigen-specific anti-cytomegalovirus antibody reactivity in patients with systemic sclerosis and concomitant anti-Ro52 antibodies.

Anti-Ro52 autoantibody (autoAb), highly prevalent in Sjogren's syndrome (SjS) and systemic lupus erythematosus (SLE), is also frequent in systemic sclerosis (SSc). Viral agents, such as human cytomegalovirus (HCMV), have been considered as a trigger for SSc and SSc-associated autoAbs. To seek for antigen-specific anti-HCMV associations with anti-Ro52, we assessed the dominant anti-HCMV ab responses in anti-Ro52 antibody (ab)-positive and -negative patients with SSc and compared them with those in SLE and SjS. 116 Anti-HCMV ab(+) sera were analyzed, including 70 from anti-Ro52(+) patients (29 SSc, 23 SLE and 18 SjS) and 46 from anti-Ro52(-) patients (29 with SSc, 9 with SLE and 8 with SjS) as negative controls. Abs against specific HCMV pp130/UL57, pp65/UL83, pp55/UL55, pp52/UL44, p38 and pp28/UL99 antigens were tested by immunoblotting. Anti-Ro52(+) SSc patients reacted more frequently against pp52/UL44 and p38 compared to anti-Ro52(-) [(13/29, 44.8%; 95% CI 26.7-62.9% vs. 1/29, 3.4%; 95% CI 0-10%, p < 0.001, and 9/29, 31.0%; 95% CI 14.2-47.8% vs. 2/29, 6.9%; 95% CI 0-16.1%, p = 0.041, respectively]. No such differences were noted between anti-Ro52(+) and anti-Ro52(-) SLE or SjS patients. Also, antibody titres against HCMV pp65/UL83, pp52/UL44 and p38 antigens were higher in anti-Ro52(+) than anti-Ro52(-) SSc patients (p < 0.01). Ab responses against specific HCMV antigens differ among anti-Ro52 ab-positive and -negative patients with SSc (as well as between SSc and SLE or SjS), but whether these differences are epiphenomenal remains to be seen.

A comprehensive analysis of antigen-specific antibody responses against human cytomegalovirus in patients with systemic sclerosis.

Anti-human cytomegalovirus (HCMV) antibodies are considered triggers of systemic sclerosis (SSc), but such a hypothesis has been assessed in limited sub-dominant epitopes. Our aim was to systematically assess the potential association of HCMV antibodies targeting most immunodominant and subdominant viral antigens, as this would reveal immunopathogenic associations. Our study included 110 SSc patients, 60 multiple sclerosis (MS) patients, and 51 healthy controls (HC). Anti-HCMV abs were tested by immunoblotting. IgG anti-HCMV was broader in SSc and MS compared to HC. Anti- UL57 and UL55 were more frequent in SSc versus MS forms. Reactivity to multiple viral antigens was more frequent in SSc than MS forms. Anti-viral antibodies levels were higher in specific autoantibody-positive SSc patients compared to seronegative cases. In conclusion, more prevalent and/or stronger antigen-specific HCMV responses are noted in SSc compared to controls, implying a role of these viral responses in SSc development.

Increased immunoreactivity against human cytomegalovirus UL83 in systemic sclerosis.

OBJECTIVES: To study immunoreactivity against human cytomegalovirus (HCMV) in systemic sclerosis (SSc), since HCMV has been put forward as a candidate infectious cause. METHODS: Eighty four patients with SSc (67 females; median age 60 years, range 25-81), 30 patients with multiple sclerosis (MS) (23 females; median age 44, range 20-69 years) and 28 healthy controls (NCs), all pre-tested positive for IgG anti-HCMV antibodies, were studied. IgG anti-UL83 HCMV antibodies were tested by western immunoblotting and expressed in arbitrary units (AUs). Reactivity to UL83 HCMV was assessed in relation to clinical manifestations and SSc-related autoantibodies (autoAbs), tested by an IgG SSc autoantibody profile line immunoassay (Euroimmun) that detects autoAbs against Scl-70, CENPA, CENPB, RNA polymerase III subunit 11 (RP11), RP155, fibrillarin, NOR90, Th/To, PM-Scl100, PM-Scl75, Ku, PDGFR and Ro-52. RESULTS: Fifty patients (59.5%) were anti-UL83 clear positive (UL83+), including 21/40 (52.5%) lcSSc and 29/44 (65.6%) dcSSc, compared to 15/30 (50%) patients with MS (SSc vs MS, p=ns and 11/28 (39.29%) of NCs (SSc vs NC, p=ns MS vs NC, p=ns). Anti-UL83 antibody AU levels (mean±SD) were higher in SSc (64.3 ± 26) compared to MS (49.1±21.6, p=0.05) or NCs (40.4±13.7, p<0.001; MS vs NCs, p=ns) and were associated with pulmonary fibrosis. CONCLUSIONS: Immunoreactivity to UL83 HCMV is frequent and strong in patients with SSc, implying a possible pathogenic role for this disease.

Functional characterisation of alpha-galactosidase a mutations as a basis for a new classification system in fabry disease.

Fabry disease (FD) is an X-linked hereditary defect of glycosphingolipid storage caused by mutations in the gene encoding the lysosomal hydrolase α-galactosidase A (GLA, α-gal A). To date, over 400 mutations causing amino acid substitutions have been described. Most of these mutations are related to the classical Fabry phenotype. Generally in lysosomal storage disorders a reliable genotype/phenotype correlation is difficult to achieve, especially in FD with its X-linked mode of inheritance. In order to predict the metabolic consequence of a given mutation, we combined in vitro enzyme activity with in vivo biomarker data. Furthermore, we used the pharmacological chaperone (PC) 1-deoxygalactonojirimycin (DGJ) as a tool to analyse the influence of individual mutations on subcellular organelle-trafficking and stability. We analysed a significant number of mutations and correlated the obtained properties to the clinical manifestation related to the mutation in order to improve our knowledge of the identity of functional relevant amino acids. Additionally, we illustrate the consequences of different mutations on plasma lyso-globotriaosylsphingosine (lyso-Gb3) accumulation in the patients' plasma, a biomarker proven to reflect the impaired substrate clearance caused by specific mutations. The established system enables us to provide information for the clinical relevance of PC therapy for a given mutant. Finally, in order to generate reliable predictions of mutant GLA defects we compared the different data sets to reveal the most coherent system to reflect the clinical situation.

Disease duration of episodic migraine correlates with modified amplitudes and habituation of contingent negative variation.

Cortical habituation in episodic migraine patients without medication overuse headache (MOH), recorded by contingent negative variation (CNV), is often reduced compared with healthy controls. There is evidence that with longer duration of migraine disease (DOD) amplitudes and habituation of CNV become progressively abnormal. The aim of the study was to examine habituation characteristics of contingent negative variation in episodic migraine patients suffering from short- and long-lasting migraine compared to matched healthy controls. 32 migraine patients without aura and without MOH diagnosed according to the revised ICHD-II criteria and 16 age- and sex-matched healthy controls were included. According to DOD, the total sample of migraine patients was divided into two groups (group a: DOD <121 months, n = 17 subjects, group b: DOD >120 months, n = 15 subjects). Both migraine groups did not differ in the number of days of migraine and the duration of attacks. Overall CNV and initial CNV differed significantly between migraine patients and controls, whereas the former produced more negative amplitudes. In the migraine group lack of or deficient habituation occurred, whilst controls showed habituation. There were middle range correlations between the DOD and overall CNV, initial CNV, and y-intercept. Patients suffering from long-lasting migraine produced higher CNV amplitudes with a higher y-intercept. The results are interpreted as "maladaptive plasticity" with a risen intercept in long-lasting migraine.

Relationship between Contingent Negative Variation and afterimage duration in migraine patients.

Background: Abnormalities in electrocortical parameters and persistence of afterimage after visual stimulation are known to occur in migraine patients. The results of studies on Contingent Negative Variation (CNV) and afterimage persistence in migraine patients suggest a link between these two phenomena and a connection to the pathomechanism of migraine. Objectives: To date, no studies have investigated both afterimage duration and CNV parameters in the same subjects. The aim of this study was to investigate the relationship between the early component of CNV (iCNV) and the duration of the afterimage in migraine patients. Methods: Sixty seven migraine patients from the headache center of the University of Rostock Medical Center were examined for iCNV amplitude, iCNV habituation and afterimage duration. The subjects also completed questionnaires developed for this study and the MIDAS (Migraine Disability Assessment) questionnaire. Results: Associations were found between iCNV amplitude and afterimage duration and between habituation capacity and afterimage duration. A deficit in habituation capacity correlated with a significantly prolonged afterimage duration. Increased iCNV amplitude and prolonged afterimage duration were also significantly correlated. Conclusion: Conclusions about the pathophysiology of migraine can be drawn from the results of this study. The results support the hypothesis of cortical hyperexcitability as a consequence of a low pre-activation level, which may be a possible contributory cause of migraine. Furthermore, they allow assessment of whether the afterimage examination, which is easier and quicker to perform than the CNV examination, can be used as a diagnostic tool or as a parameter to monitor the course of therapy in people with migraine.

Acute cerebrovascular disease in the young: the Stroke in Young Fabry Patients study.

BACKGROUND AND PURPOSE: Strokes have especially devastating implications if they occur early in life; however, only limited information exists on the characteristics of acute cerebrovascular disease in young adults. Although risk factors and manifestation of atherosclerosis are commonly associated with stroke in the elderly, recent data suggests different causes for stroke in the young. We initiated the prospective, multinational European study Stroke in Young Fabry Patients (sifap) to characterize a cohort of young stroke patients. METHODS: Overall, 5023 patients aged 18 to 55 years with the diagnosis of ischemic stroke (3396), hemorrhagic stroke (271), transient ischemic attack (1071) were enrolled in 15 European countries and 47 centers between April 2007 and January 2010 undergoing a detailed, standardized, clinical, laboratory, and radiological protocol. RESULTS: Median age in the overall cohort was 46 years. Definite Fabry disease was diagnosed in 0.5% (95% confidence interval, 0.4%-0.8%; n=27) of all patients; and probable Fabry disease in additional 18 patients. Males dominated the study population (2962/59%) whereas females outnumbered men (65.3%) among the youngest patients (18-24 years). About 80.5% of the patients had a first stroke. Silent infarcts on magnetic resonance imaging were seen in 20% of patients with a first-ever stroke, and in 11.4% of patients with transient ischemic attack and no history of a previous cerebrovascular event. The most common causes of ischemic stroke were large artery atherosclerosis (18.6%) and dissection (9.9%). CONCLUSIONS: Definite Fabry disease occurs in 0.5% and probable Fabry disease in further 0.4% of young stroke patients. Silent infarcts, white matter intensities, and classical risk factors were highly prevalent, emphasizing the need for new early preventive strategies. Clinical Trial Registration Information- URL: http://www.clinicaltrials.gov.Unique identifier: NCT00414583.

Headache as a symptom at stroke onset in 4,431 young ischaemic stroke patients. Results from the "Stroke in Young Fabry Patients (SIFAP1) study".

Headache as symptom of stroke is linked to gender, history of migraine, younger age, cerebellar stroke, and low blood pressure. These associations have been controversial, large scale studies are missing. We used the stroke in young fabry patients study to examine the association of demographic, clinical and imaging factors with the occurrence of headache in 4,431 young ischaemic stroke patients (18-55 years; mean: 44.7 years) with an ischemic cerebrovascular event (CVE) (ischemic stroke-IS 75.9%, TIA 24.1%). Headache in males occurred more frequently in bilateral localisation (right/left/bilateral: 27.5, 24.6, 39.2%, p < 0.01), but not in females (40.3, 34.7, 39.6%). Headache occurrence was more often associated in both genders with IS or TIA in the posterior cerebral territory (male: 33.2%, p < 0.05; female: 51.0%, p < 0.01) and vertebrobasilar arteries (male: 44.8%, p < 0.001; female: 51.2%, p < 0.001). The larger the size of the most prominent lesion the more likely patients were complaining headache during the IS (≤1 cm vs. >half lobe: 19.5 vs. 28.4% in male, p < 0.001; 28.9 vs. 39.1% in female, p < 0.01). Binary logistic regression analyses revealed lower age (p < 0.001), female sex (p < 0.001), larger size of the largest lesion (p < 0.001), and localization in the vertebrobasilar territory (p < 0.001) as predictors for headache during CVE. Headache at stroke onset is more common during IS in females, younger patients, with greater size of the acute lesion, and affected in posterior cerebral artery or vertebrobasilar system. Headache is a leading symptom in specific combination of stroke factors. These factors should be taken into account when patients report headache during IS or TIA.

Tuning the growth orientation of epitaxial films by interface chemistry.

The support of epitaxial films frequently determines their crystallographic orientation, which is of crucial importance for their properties. We report a novel way to alter the film orientation without changing the substrate. We show for the growth of CoO on the Ir(100) surface that, while the oxide grows in (111) orientation on the bare substrate, the orientation switches to (100) by introducing a single (or a few) monolayer(s) of Co between the oxide and substrate. This tunability of the orientation of epitaxial films by the appropriate choice of interface chemistry most likely is a general feature.

The effects of shift work on physical and mental health.

Occupational engagement is a pre-requisite for continuous income opportunities. Among the changing social circumstances work-related conditions play an increasingly eminent role in psychological and mental well-being. The public discusses the question of a possible association between the demands of modern work life and the increases of psychological, psychosomatic and cardiovascular disorders. Given the socioeconomic implications of psychiatric and psychosomatic suffering in the general population, there is a need to further elucidate the causes of their increasing incidence. From a medical point of view, any organization of work disrupting the phased circadian rhythms for bio-psycho-social processes and functioning of the individual are interesting against the background of clock genes and certain biological functions that are organized in a circadian fashion. The authors review the influence of shift work as a form of systematic desynchronization of inner clock systems on the endocrine, the physical, and the mental level. The significance of the findings in the field is discussed along with future directions of conclusive research.

Time-dependent post-imperative negative variation indicates adaptation and problem solving in migraine patients.

According to the Seligman theory of learned helplessness, depression is caused by a repetitive experience of loss of control resulting in internal, stable and global attributional styles for negative events. In depressed patients and healthy controls experiencing such events, an increased amplitude of the post-imperative negative variation (PINV) has been described. The aim of the study was to investigate a possible correlation between migraine, depression, learned helplessness and PINV. 24 patients suffering from migraine without aura and 24 healthy controls were exposed to a situation of loss of control whilst the contingent negative variation (CNV) from C3, C4 and Cz were recorded. Before conducting the experiment, the subjects were asked to answer the Beck Depression Inventory (BDI) and the German attributional style questionnaire (GASQ). Amplitudes of total CNV, early and late component and PINV were calculated in eight blocks of four recordings each. The results confirm findings of a pronounced PINV in situations of loss of control, though high amplitudes were not correlated with low values in the GASQ and therefore with learned helplessness. High PINV in migraine patients correlated with high scores in the BDI and the list of the complaints questionnaire. However, this was not the case in healthy controls. In this experimental situation, PINV in migraine patients can be interpreted as an expectancy potential in order to avoid failure and helplessness.

Cortical habituation deficit in tinnitus sufferers: contingent negative variation as an indicator of duration of the disease.

Cortical attention and habituation parameters are altered in patients suffering from tinnitus. The aim of the study was to quantify cortical attention and habituation parameters in tinnitus patients by recording the contingent negative variation (CNV) response and to correlate amplitudes of different CNV parameters with duration of disease. Twenty patients suffering from tinnitus (median: 44 years) and twenty age- and sex-matched healthy controls (median: 41 years) were tested by a CNV paradigm. We recorded overall CNV, initial CNV, and terminal CNV and calculated habituation slopes. All CNV parameters were Spearman-correlated with individual duration of disease. Highly significant between groups differences emerged in total (tinnitus: -8.4 uV vs. controls: -3.8 uV), initial (-11.2 vs. -6.0 uV), and terminal CNV (-11.9 vs. -6.5 uV) demonstrating higher negative amplitudes in tinnitus patients. Habituation differed in total and terminal CNV, indicating missing habituation in tinnitus patients. Overall CNV (ϱ = -.365) and initial CNV (ϱ = -.529) showed a medium Spearman correlation with duration of disease. We conclude that the correlation between duration of tinnitus and the initial CNV amplitudes indicates an altered state of cortical excitability that can also be observed in more negative CNV-amplitudes in tinnitus patients. We assume that this state indicates a chronicity process in tinnitus disease.

Trauma and stress-related disorders in German emergency physicians: the predictive role of personality factors.

Emergency medical personnel (EMP) are repeatedly exposed to traumatic and stressful events with possible consequences on their mental wellbeing. Out of the group of EMP, we chose German Emergency Physicians (EP), because they represent a distinct group within the German pre-hospital emergency services. In this group, we studied the prevalence rates of posttraumatic stress disorder (PTSD), burnout and depression. We specifically focussed on the role of personality and other factors of vulnerability. Four hundred eighty-seven German EPs answered questionnaires with scales assessing probable PTSD, burnout, depression, and personality factors. Additionally, we asked for biographic, occupational and mental health information. More than 90% of the participants reported at least one traumatic event. We found low to moderate levels of stress-related disorders with 16.8% of participants meeting the criteria for probable PTSD, 4.1% for burnout, and 3.1% for clinical depression. We identified four clusters of personalities that were related to the prevalence of PTSD and depression. The type of personality seems to be more predictive of the development of trauma and stress-related disorders than the EPs' traumatic experiences.

Atmospheric ozone and colors of the Antarctic twilight sky.

Zenith skylight is often distinctly blue during clear civil twilights, and much of this color is due to preferential absorption at longer wavelengths by ozone's Chappuis bands. Because stratospheric ozone is greatly depleted in the austral spring, such decreases could plausibly make Antarctic twilight colors less blue then, including at the zenith. So for several months in 2005, we took digital images of twilight zenith and antisolar skies at Antarctica's Georg von Neumayer Station. Our colorimetric analysis of these images shows only weak correlations between ozone concentration and twilight colors. We also used a spectroradiometer at a midlatitude site to measure zenith twilight spectra and colors. At both locations, spectral extinction by aerosols seems as important as ozone absorption in explaining colors seen throughout the twilight sky.

Anti-Ro52 antibody is highly prevalent and a marker of better prognosis in patients with ovarian cancer.

BACKGROUND AND AIMS: Anti-Ro52 antibody (Ab) reactivity is highly prevalent in autoimmune rheumatic diseases (ARDs), mainly Sjögren's syndrome (SjS) and systemic lupus erythematosus (SLE), but also in other inflammatory disorders. Thorough assessment of the prevalence, clinical significance and epitope specificity of Ro52-autoAbs in cancerous diseases is still lacking. MATERIAL AND METHODS: Anti-Ro52 Ab reactivity was tested in a large cohort of 490 patients with various malignant diseases. Ro52-autoAb epitope mapping by an in house line immunoassay was carried out using 5 recombinant Ro52 polypeptides spanning Ro52. RESULTS: Anti-Ro52 abs were significantly more prevalent in patients with ovarian cancer (30%) compared to patients with 6 other malignant diseases (median 8.1%, range 5.9-15.8%). The presence of anti-Ro52 abs in patients with ovarian cancer was strongly associated with better overall survival. Ro52 epitope mapping of patients with ovarian cancer was dissimilar to that of SLE and SjS ARDs, less frequently recognizing Ro52-1 and Ro52-4 fragments compared to patients with SLE and SjS. CONCLUSION: We demonstrate for first time an unexpectedly high frequency of anti-Ro52 abs in patients with ovarian cancer, their presence indicating better overall survival. Their distinguishing epitope profile may suggest a non-SLE or SjS-related stimulus for autoAb production.

Regional impairment of 18F-FDG uptake in the cervical spinal cord in patients with monosegmental chronic cervical myelopathy.

OBJECTIVE: The aim of this preliminary report was to assess glucose metabolism in the cervical spine of patients with chronic compressive myelopathy by using FDG PET. METHODS: Ten patients with monosegmental chronic degenerative stenosis and local cord compression of the upper/middle cervical spine with signs of myelopathy on MRI and 10 control patients without known cervical abnormalities were investigated by FDG PET. Maximum standardised uptake values (SUV(max)) were measured at all levels of the cervical spine (C1-C7). RESULTS: While the controls showed the typical pattern of homogeneous linear FDG uptake along the entire cervical cord, the patients with chronic compressive myelopathy had a normal glucose utilisation only above the level of stenosis and a significant decrease in FDG uptake below their individual level of cord compression. This may be caused by atrophy of anterior grey horn cells and the loss of glucose-consuming neurons below the level of cord compression. CONCLUSION: FDG PET of the spine of patients with chronic compressive myelopathy may be helpful to determine the stage and severity of cervical myelopathy.

A comprehensive analysis of antigen-specific autoimmune liver disease related autoantibodies in patients with multiple sclerosis.

INTRODUCTION: Abnormal liver function tests are frequently seen in patients with multiple sclerosis (MS) and their origin at times is attributed to the possible co-occurrence or the de novo induction of autoimmune liver diseases (AILD), namely autoimmune hepatitis (AIH) and primary biliary cholangitis (PBC), but comprehensive analysis of AILD-related autoantibody has not been carried out. AIM: To assess the presence of AILD-related autoantibodies in a well-defined cohort of MS patients, and to assess their clinical significance. MATERIALS AND METHODS: 133 MS (93 female) patients (102 RRMS, 27 SPMS, and 5 PPMS), mean age 42.7 ± 11.9 SD years, mean duration of disease 11.2 ± 7.2 years were studied. 150 age and sex-matched healthy individuals were tested as normal controls (NCs).Autoantibody testing was performed by indirect immunofluorescence (IF) using triple tissue and HEp-2, a multiparametric line immunoassay detecting anti-LKM1(anti-CYP2D6), anti-LC1(anti-FTCD), soluble liver antigen/liver-pancreas(anti-SLA/LP), AMA-M2, and AMA-MIT3 (BPO), PBC-specific ANA (anti-gp210, anti-sp100 and anti-PML), and ELISA for anti-F-actin SMA and anti-dsDNA antibodies. RESULTS: Reactivity to at least one autoantibody was more frequent in MS patients compared to NCs (30/133, 22.6% vs 12/150, 8%) NCs (p = 0.00058). SMAs by IIF were more frequent in MS patients (18/133, 13.53%) compared to NCs (6/150, 4%, p = 0.002%). The AIH-1 related anti-F-actin SMA by ELISA were present in 21 (15.8%), at relatively low titres (all but three of the SMA-VG pattern by IF); anti-dsDNA in 3 (2.3%), and anti-SLA/LP in none; AIH-2 anti-LKM1 autoantibodies in 1 (0.8%, negative by IF), and anti-LC1 in none; PBC-specific AMA-M2 in 2 (1.5%, both negative for AMA-MIT3 and AMA by IF) and PBC-specific ANA anti-PML in 6 (4.5%), anti-sp100 in 1 (0.8%) and anti-gp210 in 1 (0.8%). Amongst the 30 MS patients with at least one autoantibody positivity, only 4 (3%) had overt AILD (2 AIH-1 and 2 PBC). Autoantibody positivity did not differ between naïve MS patients and patients under treatment. CONCLUSIONS: Despite the relatively frequent presence of liver autoantibodies, tested either by IF or molecular assays, overt AILD is rather infrequent discouraging autoantibody screening strategies of MS patients in the absence of clinical suspicion.

Effects of IVIg treatment on autoantibody testing in neurological patients: marked reduction in sensitivity but reliable specificity.

BACKGROUND: Therapy of autoimmune diseases of the central and peripheral nervous system with intravenous IgG immunoglobulin (IVIg) is well established. Since IVIg is produced from pooled human plasma, autoantibodies can be found in IVIg products and, accordingly, in patient sera after transfusion. The de novo evidence or disappearance of anti-neural autoantibodies after IVIg treatment has so far not been systematically examined. METHODS: We screened 50 neurological patients before and after IVIg treatment for classical onconeural and the most common neurological surface autoantibodies as well as for ganglioside autoantibodies and 23 different antinuclear autoantibodies using immunoblot or cell-based indirect immunofluorescence assays. Furthermore, we screened 31 neurological patients with previously known seropositivity for disappearance of the corresponding antibody after treatment. RESULTS: After IVIg treatment, 90% of all sera were de novo positive for antinuclear antibodies, especially for Ro-52. In contrast, 94% of all sera did not show any de novo-positive anti-neural antibodies. In the remaining three cases, titers were very low. Importantly, 12.9% of all tested sera of patients with known antibody positivity turned false negative after IVIg treatment and titers were falsely low in 37% of the remaining sera. CONCLUSIONS: Here, we present for the first time results of a broad screening for clinically relevant autoantibodies before and after IVIg treatment in neurological patients. We identified a high specificity but reduced sensitivity for anti-neural antibody testing after IVIg transfusion. In contrast, antinuclear antibody testing is not reliable after IVIg treatment. These results are of high practical importance for diagnostic of neuroimmunological diseases.

Antigen-specific humoral responses against Helicobacter pylori in patients with systemic sclerosis.

Helicobacter pylori (Hp) is a likely trigger of systemic sclerosis (SSc), but systemic antigen-specific antibody (Ab) responses in a well-defined cohort of SSc patients have not been thoroughly assessed. Line immunoassay and immunoblotting testing Abs against 15 Hp antigens were performed in 91 SSc patients and 59 demographically matched healthy controls (HCs). Results were validated in an independent cohort of 35 SSc patients. Anti-Hp positivity was detected in 67% SSc patients vs 76.3% HCs. Among anti-Hp (+) individuals, anti-p67-FSH was less frequent in SSc than HCs (p = 0.016), whereas reactivity to the remaining 14 Hp antigens did not differ between patients and HCs. Anti-p67 Abs were less frequent in diffuse cutaneous SSc (dcSSc) compared with HCs (p = 0.018). Anti-p57 and anti-p33 Ab levels were lower in SSc vs HCs (p = 0.007 and p = 0.035, respectively). Anti-p57 and anti-p33 Ab levels were lower in limited cutaneous SSc (lcSSc) (p = 0.010) and dcSSc (p = 0.024), respectively, compared with HCs. Anti-p50 and anti-p17 Ab titers tended to be higher in dcSSc than in lcSSc. Sera from the independent SSc cohort showed comparable results. Anti-VacA Abs were more frequent in pulmonary arterial hypertension (p = 0.042), and anti-p30 Abs were more frequent in calcinosis (p = 0.007), whereas anti-VacA Ab levels were higher in lung fibrosis (p = 0.02). In conclusion, anti-Hp Abs are neither more frequent nor elevated in SSc compared with healthy population, the only exception being the higher frequency and levels of anti-VacA Abs in pulmonary hypertension and lung fibrosis, respectively. These results suggest that Hp is unlikely to be involved in the development of SSc.

Autoantibodies against specific nuclear antigens are present in psoriatic disease and are diminished by secukinumab.

Anti-nuclear antibodies (ANA) are frequently detected in patients with psoriasis (Ps) and psoriatic arthritis (PsA), but their target autoantigens remain unknown. We assessed antibody (ab) reactivity against 23 known nuclear antigens in patients with Ps and PsA and assess the effects of secukinumab (anti-IL17A) treatment on ANA levels. A total of 201 patients, 101 with Ps and 100 with PsA, and 50 ANA-negative healthy controls (HCs) were tested for ANAs by a line immunoassay testing reactivity to 23 nuclear antigens. Ab reactivity to at least 1 antigen was found in 20.4% psoriatic disease patients (25.7% Ps and 15% PsA) compared to 8% HCs (p = ns), the most frequent being against dense fine speckled 70 (DFS70) (6.5%). In Ps and PsA patients with secukinumab-induced remission, anti-DFS70 and other antigen-specific autoantibodies were diminished over time. No decline was noted for IgG abs against antigens from pathogens such as cytomegalovirus, Epstein-Barr virus and Helicobacter pylori. Autoantibody decrease was associated with significant reduction of plasmablasts, follicular B and follicular T cells. In conclusion, one third of antigen-specific ANA patients with psoriatic disease recognize DFS70. Secukinumab decreases nuclear antigen autoreactivity, plasmablasts, follicular B and follicular T cells, highlighting a new mechanism of its action.