The relationship of HLA-G 14-bp insertion/deletion genetic polymorphism to the risk of multiple sclerosis and its clinical phenotypes

Abstract Background Human leukocyte antigen (HLA)-G molecule has been suggested to have a potential immunomodulatory role in multiple sclerosis (MS). Genetic variant sites of HLA-G molecule have been reported to be associated with autoimmune diseases. Identifying the genetic risk factors of MS may help in preventive strategies and anticipating disease progression. The aim of this work was to investigate the effect of HLA-G 14-base-pair insertion/deletion (14-bp INS/DEL) genetic polymorphism on MS risk and clinical characteristics and to observe the clinical characteristics of the MS patients’ group. The study included 48 MS patients and 50 cross-matched healthy controls, who were recruited from Sohag and Assiut university hospitals. Genetic testing (14-bp Ins/Del gene polymorphism) using polymerase chain reaction (PCR) was performed for patients and control groups. All patients had a detailed clinical assessment and have undergone measurement of disability using the Expanded Disability Status Scale (EDSS). Results No statistically significant difference was found between MS patients and healthy controls (HC) in genotypic and allelic frequencies of HLA-G 14-bp INS/DEL polymorphism (P=0.305). No significant association was found between HLA-G 14-bp INS/DEL polymorphism genotypes and clinical characteristics or degree of disability of MS patients. The most frequent presenting symptoms of MS were motor symptoms. Fatigue was the most reported symptom along the course of MS disease. Conclusion Although it has been long known that HLA-G represents an important MS susceptibility locus, in this study, no significant relation could be detected between the 14-bp INS/DEL polymorphism genotype and MS susceptibility. MS risk susceptibility may be not linked to a single allele but may depend on the combination of different polymorphic genetic sites. In this study, the lack of genetic susceptibility may be attributed to ethnic factor.

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Multiple Sclerosis and Diabetes Mellitus: Further Evidence of a Relationship

Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques ◽

10.1017/s0317167100044322 ◽

1982 ◽

Vol 9 (4) ◽

pp. 415-419 ◽

Cited By ~ 14

Author(s):

Sharon A. Warren ◽

K.G. Warren

Keyword(s):

Diabetes Mellitus ◽

Multiple Sclerosis ◽

Healthy Controls ◽

Degree Relative ◽

Significant Difference ◽

The Difference ◽

The Relationship ◽

Prevalence Of Diabetes Mellitus ◽

Second Degree

SUMMARY:One hundred multiple sclerosis (MS) patients were compared to healthy controls to determine the prevalence of diabetes mellitus in their families. Significantly, more MS patients than controls were diabetic or reported at least one first degree relative (parent, sibling, child) with diabetes. The relationship between MS and diabetes persisted when second degree relatives (grandparents, aunts and uncles) were taken into consideration.A greater percentage of MS patients with another MS relative were diabetic or reported a first degree relative with diabetes mellitus than MS patients without an MS relative. However the difference was not statistically significant. Nor was there a significant difference when percentages reporting either a first or a second degree relative with diabetes were compared.

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Early Cognitive Impairment in Multiple Sclerosis Patients In Relation To Brain Atrophy, Egyptian Sample

QJM ◽

10.1093/qjmed/hcaa054.008 ◽

2020 ◽

Vol 113 (Supplement_1) ◽

Author(s):

M F Zakaria ◽

T A Abdo ◽

A A Abdelaziz ◽

D A Zamzam ◽

Y A Abdullah ◽

...

Keyword(s):

Multiple Sclerosis ◽

Cognitive Impairment ◽

Brain Atrophy ◽

General Medicine ◽

Economic Consequences ◽

University Hospitals ◽

Cross Sectional ◽

Significant Difference ◽

Multiple Sclerosis Patients

Abstract Background Approximately half of all patients with multiple sclerosis (MS) experience cognitive impairment, most commonly with regard to new learning and memory. Cognitive dysfunction is a leading cause of disability in MS and it can have profound social and economic consequences for patients and their families. Objective This study was conducted to discover the early cognitive domains affected in multiple sclerosis patients concomitant with the postulated brain atrophy in an Egyptian sample of multiple sclerosis patients. Patients and Methods A cross-sectional observational case-control study conducted on seventy (60) patients who came for follow-up in Ain Shams University hospitals. 40 patients were taken as cases that followed up in MS unit in Ain-Shams university hospitals. 20 participants were taken as controls taken from the general medicine clinics age and sex matched to our patient group. An informed written consent was taken from parents of each person included in the study. Results There was a statistically significant difference between the two groups in brain volumetric changes and in the parameters of cognitive assessment Conclusion Early detection and examination of cognitive functions is important for patient evaluation, follow up and treatment regimen used.

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Orbital Apex Lesions: A Diagnostic and Therapeutic Challenge

Journal of Neurological Surgery Part B Skull Base ◽

10.1055/s-0037-1612616 ◽

2017 ◽

Vol 79 (04) ◽

pp. 386-393 ◽

Cited By ~ 3

Author(s):

Sung-Woo Cho ◽

Won-Wook Lee ◽

Dae Ma ◽

Ji-hoon Kim ◽

Doo Han ◽

...

Keyword(s):

Treatment Outcomes ◽

Clinical Characteristics ◽

Inflammatory Pseudotumor ◽

Definitive Treatment ◽

Fungal Sinusitis ◽

Orbital Apex ◽

Radiological Findings ◽

Presenting Symptoms ◽

Invasive Fungal Sinusitis ◽

Significant Difference

Objective To analyze the clinical characteristics of and treatment outcomes for orbital apex lesions according to their pathological diagnosis and identify clinical characteristics that could aid in their differential diagnosis. Design Retrospective analysis design was used for this study. Setting The study was conducted in a single tertiary institution. Participants Patients with pathologically confirmed lesions centered in the orbital apex who were admitted between January 2011 and December 2015. Main Outcome Measures Clinical characteristics, including demographics, predisposing factors, presenting symptoms, radiological findings, intraoperative findings, biopsy results, and treatment outcomes. Results Nine patients with invasive fungal sinusitis, six with inflammatory pseudotumor, and six with neoplastic or tumorous lesions were enrolled. The most common presenting symptom was orbital pain or headache, followed by ophthalmoplegia and vision loss, which exhibited overall recovery rates of 62.5% and 33.3%, respectively, after definitive treatment. The prognosis was worse for patients with invasive fungal sinusitis. There was no significant difference in age, underlying medical conditions, absolute neutrophil count, C-reactive protein level, and radiological findings among the three groups. Grossly necrotic tissues around the orbital apex area at biopsy were more frequently found in patients with invasive fungal sinusitis than in the other patients. In most cases, pain ameliorated after surgical intervention. There were no surgery-related morbidities. Conclusions Lesions centered in the orbital apex included invasive fungal sinusitis, inflammatory pseudotumor, and tumorous lesions. However, clinical features that clearly differentiated chronic invasive fungal sinusitis from inflammatory pseudotumor could not be identified. Our findings suggest that prompt biopsy is warranted for timely diagnosis, symptom relief, and early implementation of definitive treatment.

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Quantification of human plasma metalloproteins in multiple sclerosis, ischemic stroke and healthy controls reveals an association of haptoglobin-hemoglobin complexes with age

PLoS ONE ◽

10.1371/journal.pone.0262160 ◽

2022 ◽

Vol 17 (1) ◽

pp. e0262160

Author(s):

Sophia Sarpong-Kumankomah ◽

Katherine B. Knox ◽

Michael E. Kelly ◽

Gary Hunter ◽

Bogdan Popescu ◽

...

Keyword(s):

Multiple Sclerosis ◽

Ischemic Stroke ◽

Inductively Coupled Plasma ◽

Rank Correlation ◽

Positive Association ◽

Disease Diagnosis ◽

Size Exclusion ◽

Control Group ◽

Healthy Controls ◽

Significant Difference

Advanced analytical methods play an important role in quantifying serum disease biomarkers. The problem of separating thousands of proteins can be reduced by analyzing for a ‘sub-proteome’, such as the ‘metalloproteome’, defined as all proteins that contain bound metals. We employed size exclusion chromatography (SEC) coupled to an inductively coupled plasma atomic emission spectrometer (ICP-AES) to analyze plasma from multiple sclerosis (MS) participants (n = 21), acute ischemic stroke (AIS) participants (n = 17) and healthy controls (n = 21) for Fe, Cu and Zn-metalloproteins. Using ANOVA analysis to compare the mean peak areas among the groups revealed no statistically significant differences for ceruloplasmin (p = 0.31), α2macroglobulin (p = 0.51) and transferrin (p = 0.31). However, a statistically significant difference was observed for the haptoglobin-hemoglobin (Hp-Hb) complex (p = 0.04), being driven by the difference between the control group and AIS (p = 0.012), but not with the MS group (p = 0.13), based on Dunnes test. A linear regression model for Hp-Hb complex with the groups now adjusted for age found no statistically significant differences between the groups (p = 0.95), but was suggestive for age (p = 0.057). To measure the strength of association between the Hp-Hb complex and age without possible modifications due to disease, we calculated the Spearman rank correlation in the healthy controls. The latter revealed a positive association (r = 0.39, 95% Confidence Interval = (-0.05, 0.83), which suggests that either the removal of Hp-Hb complexes from the blood circulation slows with age or that the release of Hb from red blood cells increases with age. We also observed that the Fe-peak corresponding to the Hp-Hb complex eluted ~100 s later in ~14% of all study samples, which was not correlated with age or disease diagnosis, but is consistent with the presence of the smaller Hp (1–1) isoform in 15% of the population.

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Long-term follow-up of clinical presentation and outcomes of patients with urinary bladder paragangliomas.

Journal of Clinical Oncology ◽

10.1200/jco.2018.36.6_suppl.507 ◽

2018 ◽

Vol 36 (6_suppl) ◽

pp. 507-507

Author(s):

Kareem Rayn ◽

Michael Daniel Weintraub ◽

Gustavo Pena-LaGrave ◽

Samuel Gold ◽

Graham R. Hale ◽

...

Keyword(s):

Urinary Bladder ◽

Symptom Onset ◽

Clinical Characteristics ◽

Cancer Recurrence ◽

Plasma Catecholamine ◽

Presenting Symptoms ◽

Surgical Methods ◽

Significant Difference ◽

Long Term Follow Up ◽

Metastatic Sites

507 Background: Urinary bladder paragangliomas (UBPGLs) are extremely rare, accounting for less than 6% of paragangliomas (PGLs) and 0.06% of bladder tumors. The goal of this study is to examine the presentation, clinical characteristics and outcomes of patients with UBPGLs. Methods: We determined the presenting symptoms, clinical characteristics, and outcomes of patients who presented to a single institution with UBPGLs from 2000-2017. Results: 28 patients with an average age of 27 ± 15.6 at symptom onset presented to the NIH from 2000-2017. The majority had standard paraganglioma symptoms (n = 24, 85.7%) defined as headaches, palpitations, pallor and anxiety, and hypertension (n = 20, 71.4%) on presentation. 8 patients (29%) presented with hematuria; hematuria was the only presenting symptom in 1 of these patients. 3 (10.7%) of the patients were completely asymptomatic and were discovered to have bladder paragangliomas incidentally on imaging. Overall, 9 patients (32%) were under 18 (average age = 10.9 ± 3.9) at symptom onset. 14 (50%) patients developed metastasis, with bone (n = 9) and lung (n = 8) being the most common metastatic sites. All but 1 patient received surgical treatment, with 6 patients receiving transurethral resection of bladder tumor (TURBT), 3 receiving robotic-assisted partial cystectomy (RAPC) and the remaining patients undergoing open cystectomy. In total, 2 patients experienced bladder cancer recurrence, both of whom had undergone TURBT. Comparing patients with and without hematuria, metastasis and standard paraganglioma symptoms, we found no statistically significant difference in mean diameter of the largest lesion or plasma catecholamine values. Conclusions: Our experience reveals that most patients with UBPGLs present at an early age with characteristic paraganglioma symptoms. Despite the variety of surgical methods used to manage these patients, the only 2 recurrences were in patients who underwent TURBT. Further work is necessary to establish preoperative indicators of disease severity in patients with UBPGLs. This research was supported by the Intramural Research Program of the National Cancer Institute, NIH and NIH Medical Research Scholars Program

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HLA Class II Genotype Does Not Affect the Myelin Responsiveness of Multiple Sclerosis Patients

Cells ◽

10.3390/cells9122703 ◽

2020 ◽

Vol 9 (12) ◽

pp. 2703

Author(s):

Judith Derdelinckx ◽

Irene Nkansah ◽

Naomi Ooms ◽

Laura Van Bruggen ◽

Marie-Paule Emonds ◽

...

Keyword(s):

Multiple Sclerosis ◽

Specific Treatment ◽

Human Leukocyte ◽

Class Ii ◽

Hla Class Ii ◽

Specific Response ◽

Healthy Controls ◽

Treatment Approaches ◽

Risk Alleles ◽

Multiple Sclerosis Patients

Background: When aiming to restore myelin tolerance using antigen-specific treatment approaches in MS, the wide variety of myelin-derived antigens towards which immune responses are targeted in multiple sclerosis (MS) patients needs to be taken into account. Uncertainty remains as to whether the myelin reactivity pattern of a specific MS patient can be predicted based upon the human leukocyte antigen (HLA) class II haplotype of the patient. Methods: In this study, we analyzed the reactivity towards myelin oligodendrocyte glycoprotein (MOG), myelin basic protein (MBP) and proteolipid protein (PLP) peptides using direct interferon (IFN)-γ enzyme-linked immune absorbent spot (ELISPOT). Next, the HLA class II haplotype profile was determined by next-generation sequencing. In doing so, we aimed to evaluate the possible association between the precursor frequency of myelin-reactive T cells and the HLA haplotype. Results: Reactivity towards any of the analyzed peptides could be demonstrated in 65.0% (13/20) of MS patients and in 60.0% (6/10) of healthy controls. At least one of the MS risk alleles HLA-DRB1*15:01, HLA-DQA1*01:02 and HLA-DQB1*06:02 was found in 70.0% (14/20) of patients and in 20.0% (2/10) of healthy controls. No difference in the presence of a myelin-specific response, nor in the frequency of myelin peptide-reactive precursor cells could be detected among carriers and non-carriers of these risk alleles. Conclusion: No association between HLA haplotype and myelin reactivity profile was present in our study population. This complicates the development of antigen-specific treatment approaches and implies the need for multi-epitope targeting in an HLA-unrestricted manner to fully address the wide variation in myelin responses and HLA profiles in a heterogeneous group of MS patients.

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Increased anti-KIR4.1 antibodies in multiple sclerosis: Could it be a marker of disease relapse?

Multiple Sclerosis Journal ◽

10.1177/1352458514551779 ◽

2014 ◽

Vol 21 (5) ◽

pp. 572-579 ◽

Cited By ~ 22

Author(s):

Livnat Brill ◽

Lotem Goldberg ◽

Arnon Karni ◽

Panayiota Petrou ◽

Oded Abramsky ◽

...

Keyword(s):

Multiple Sclerosis ◽

Potassium Channel ◽

Functional Properties ◽

Clinical Characteristics ◽

Serum Levels ◽

Demyelinating Diseases ◽

Enzyme Linked Immunosorbent Assay ◽

Healthy Controls ◽

Disease Relapse ◽

Disease Exacerbation

Background: Screening of putative autoimmune targets in multiple sclerosis (MS) revealed a proportion of patients carrying antibodies (Abs) against KIR4.1, a potassium channel that shares functional properties with AQP4. Both are localized at the perivascular astrocytic processes. Aims: To measure anti-KIR4.1 Abs in the serum of MS and neuromyelitis optica (NMO) patients, and to identify the clinical and laboratory characteristics of patients harboring anti-KIR4.1 Abs. Methods: We measured anti-KIR4.1 Abs in serum, using the peptide KIR4.1 (83–120) enzyme-linked immunosorbent assay (ELISA). Results: Serum levels of anti-KIR4.1 Abs were significantly higher in MS and NMO patients than in healthy controls (HCs); with Abs detected in 21 of 80, 10 of 45, and 2 of 32 individuals, respectively (MS versus HC, p < 0.05). The level of anti-KIR4.1 Abs was significantly higher during MS relapse, versus remission ( p = 0.04). The clinical characteristics of our study patients did not vary based on KIR4.1 positivity. Conclusions: Anti-KIR4.1 Abs were found in similar proportions of patients with MS and NMO, at a significantly higher level than observed in HCs; consequently, the presence of Abs does not discriminate between these demyelinating diseases. However, anti-KIR4.1 Ab levels differed in MS patients during relapse and remission; as such, they may represent a marker of disease exacerbation.

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The Assessment of Serum Concentrations of AGEs and Their Soluble Receptor (sRAGE) in Multiple Sclerosis Patients

Brain Sciences ◽

10.3390/brainsci11081021 ◽

2021 ◽

Vol 11 (8) ◽

pp. 1021

Author(s):

Aleksandra Damasiewicz-Bodzek ◽

Beata Łabuz-Roszak ◽

Bartłomiej Kumaszka ◽

Bartosz Tadeusiak ◽

Krystyna Tyrpień-Golder

Keyword(s):

Multiple Sclerosis ◽

Stable Phase ◽

Enzyme Linked Immunosorbent Assay ◽

Control Group ◽

Healthy Controls ◽

Soluble Receptor ◽

Serum Concentrations ◽

Degree Of Disability ◽

The Mean ◽

Multiple Sclerosis Patients

Background: Advanced glycation end products (AGEs) are involved in the pathogenesis of many diseases, including neurodegenerative diseases such as multiple sclerosis (MS). The aim of the study was to determine serum concentrations of AGEs and their soluble receptor (sRAGE) in MS patients and healthy controls and to investigate their possible influence on disease activity. Methods: Serum concentrations of AGE and sRAGE in patients with MS and healthy controls were determined by enzyme-linked immunosorbent assay (ELISA). Results: The mean serum AGE concentration in patients with MS was higher than in healthy controls, whereas the mean serum sRAGE concentration was lower than in the control group. However, the differences were not statistically significant. In MS patients, serum AGE and sRAGE concentrations did not differ significantly, depending on the duration of the disease and the Expanded Disability Status Scale (EDSS) score. Conclusions: Multiple sclerosis may be accompanied by disturbances of the AGE-sRAGE axis. However, further studies are warranted to confirm it. The duration of the disease and the degree of disability do not seem to affect the progression of the glycation process, particularly in the stable phase of the disease.

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COVID-19 in Multiple Sclerosis Patients and Risk Factors for Severe Infection

10.1101/2020.05.27.20114827 ◽

2020 ◽

Cited By ~ 2

Author(s):

Farhan Chaudhry ◽

Helena Bulka ◽

Anirudha S. Rathnam ◽

Omar M Said ◽

Jia Lin ◽

...

Keyword(s):

Multiple Sclerosis ◽

Hospital Admission ◽

Clinical Characteristics ◽

Severe Infection ◽

Progressive Multiple Sclerosis ◽

Disease Modifying Therapy ◽

Degree Of Disability ◽

Significant Disability ◽

Disease Modifying ◽

Multiple Sclerosis Patients

AbstractImportanceMultiple sclerosis patients have been considered a higher-risk population for COVID-19 due to the high prevalence of disability and disease-modifying therapy use; however, no study has identified clinical characteristics of multiple sclerosis associated with worse COVID-19 outcomes.ObjectiveTo evaluate the clinical characteristics of multiple sclerosis, including staging, degree of disability, and disease-modifying therapy use that are associated with worse outcomes from COVID-19.DesignProspective cohort study looking at the outcomes of multiple sclerosis patients with COVID-19 between March 1st and May 18th 2020.SettingThis is a multicenter study of three distinct hospital systems within the U.S.ParticipantsThe study included 40 consecutive patients with nasopharyngeal/oropharyngeal PCR-confirmed COVID-19 infection.ExposuresMultiple sclerosis staging, severe disability (based on baseline-extended disability status scale equal to or greater than 6.0) and disease-modifying therapy.Main Outcomes and MeasureSeverity of COVID-19 infection was based on hospital course, where a mild course was defined as the patient not requiring hospital admission, moderate severity was defined as the patient requiring hospital admission to the general floor only, and most severe was defined as requiring intensive care unit admission and/or death.ResultsFor the 40 patients, the median age was 52(45.5-61) years, 16/40(40%) were male, and 21/40(52.5%) were African American. 19/40(47.5%) had mild courses, 15/40(37.5%) had moderate courses, and 6/40(15%) had severe courses. Patients with moderate and severe courses were significantly older than those with a mild course (57[50-63] years old and 66[58.8-69.5] years old vs 48[40-51.5] years old, P=0.0121, P=0.0373). There was differing prevalence of progressive multiple sclerosis staging in those with more severe courses (severe:2/6[33.3%]primary-progressing and 0/6[0%]secondary-progressing, moderate:1/14[7.14%] and 5/14[35.7%] vs mild:0/19[0%] and 1/19[5.26%], P=0.0075, 1 unknown). Significant disability was found in 1/19(5.26%) mild course-patients, but was in 9/15(60%, P=0.00435) of moderate course-patients and 2/6(33.3%, P=0.200) of severe course-patients. Disease-modifying therapy prevalence did not differ among courses (mild:17/19[89.5%], moderate:12/15[80%] and severe:3/6[50%], P=0.123).Conclusions and RelevanceMultiple sclerosis patients with more severe COVID-19 courses tended to be older, were more likely to suffer from progressive staging, and had a higher degree of disability. However, disease-modifying therapy use was not different among courses.

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Clinical Characteristics of Children with COVID-19: A Multicenter Study in the United Arab Emirates (Preprint)

10.2196/preprints.29049 ◽

2021 ◽

Author(s):

Farah Ennab ◽

Mariam ElSaban ◽

Eman Khalaf ◽

Hanieh Tabatabaei ◽

Amar Hassan Khamis ◽

...

Keyword(s):

United Arab Emirates ◽

Multicenter Study ◽

Clinical Characteristics ◽

Pediatric Population ◽

Contact Tracing ◽

Severe Illness ◽

Published Data ◽

Presenting Symptoms ◽

Asymptomatic Children ◽

Significant Difference

BACKGROUND Coronavirus disease 2019 (COVID-19) has infected over 123 million people globally. The first confirmed case in the United Arab Emirates (UAE) was reported on 29th January 2020. COVID-19 has fared mildly in the pediatric population according to available literature out of early epicenters of the pandemic. To date there is a lack of published data about COVID-19 infection among children in the Arabian region. OBJECTIVE Investigate the clinical characteristics, laboratory findings, treatment, and outcomes of children with COVID-19. METHODS This cross-sectional multicenter study included children with confirmed COVID-19 infection admitted between March 1st and June 15th, 2020 to three large hospitals in Dubai, UAE. Serial COVID-19 polymerase chain reaction (PCR) testing was collected, and patients' demographics, pre-morbid clinical characteristics and inpatient hospital course were investigated. RESULTS 111 children were included in our study and represented 22 nationalities. Fifty-nine (53.2%) were boys. The mean age was 7 years (±5.3). 15.3% of children were younger than 1 year. Only 4 (3.6%) of the patients had pre-existing asthma all of whom had uneventful courses. At presentation 43 (38.7%) were asymptomatic, 68 (61.2%) had mild or moderate symptoms and none had severe illness requiring intensive care. Fever (20.7%), cough (19.8%) and rhinorrhea (15.3%) were the most common presenting symptoms and most symptoms resolved by day 5 of hospitalization. Most patients had no abnormality on chest x-ray. The most common laboratory abnormalities on admission included variations in neutrophil count (24.7%), aspartate transaminase (22.5%), alkaline phosphatase (36.7%) and lactate dehydrogenase (42.5%). Children were infrequently prescribed targeted medications, with only 4 (3.6%) receiving antibiotics. None of the 52 patients tested for viral co-infections were positive. COVID-19 PCR turned negative at a median of 10 days [6-14] after first positive test. Overall, there was no significant difference of time to negative PCR results between symptomatic and asymptomatic children. CONCLUSIONS This study of COVID19 presentations and characteristics presents a first look into the burden of COVID19 infection in the pediatric population in the UAE. We conclude that a large percentage of children experienced no symptoms, and severe disease is uncommon in the UAE. Various laboratory abnormalities were observed despite clinical stability. Ongoing surveillance, contact tracing and public health measures will be important to contain future outbreaks.

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