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Vitamin D status in patients with systemic lupus erythematosus (SLE): A systematic review and meta-analysis

Islam MA, Khandker SS, Alam SS, Kotyla P, Hassan R

Autoimmun Rev, 2019 Sep 11.
PMID: 31520805 DOI: 10.1016/j.autrev.2019.102392

BACKGROUND: Systemic lupus erythematosus (SLE) is a systemic autoimmune disease where chronic inflammation and tissue or organ damage is observed. Due to various suspected causes, inadequate levels of vitamin D (a steroid hormone with immunomodulatory effects) has been reported in patients with SLE, however, contradictory.
AIMS: The aim of this systematic review and meta-analysis was to evaluate the serum levels of vitamin D in patients with SLE in compared to healthy controls.
METHODS: PubMed, SCOPUS, ScienceDirect and Google Scholar electronic databases were searched systematically without restricting the languages and year (up to March 2, 2019) and studies were selected based on the inclusion criteria. Mean difference (MD) along with 95% confidence intervals (CI) were used and the analyses were carried out by using a random-effects model. Different subgroup and sensitivity analyses were conducted. Study quality was assessed by the modified Newcastle-Ottawa Scale (NOS) and publication bias was evaluated by a contour-enhanced funnel plot, Begg's and Egger's tests.
RESULTS: We included 34 case-control studies (2265 SLE patients and 1846 healthy controls) based on the inclusion criteria. Serum levels of vitamin D was detected significantly lower in the SLE patients than that in the healthy controls (MD: -10.44, 95% CI: -13.85 to -7.03; p 
Fulltext Immunomodulatory Effects of Diet and Nutrients in Systemic Lupus Erythematosus (SLE): A Systematic Review

Islam MA, Khandker SS, Kotyla PJ, Hassan R

Front Immunol, 2020;11:1477.
PMID: 32793202 DOI: 10.3389/fimmu.2020.01477

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by multiple organ involvement, including the skin, joints, kidneys, lungs, central nervous system and the haematopoietic system, with a large number of complications. Despite years of study, the etiology of SLE remains unclear; thus, safe and specifically targeted therapies are lacking. In the last 20 years, researchers have explored the potential of nutritional factors on SLE and have suggested complementary treatment options through diet. This study systematically reviews and evaluates the clinical and preclinical scientific evidence of diet and dietary supplementation that either alleviate or exacerbate the symptoms of SLE. For this review, a systematic literature search was conducted using PubMed, Scopus and Google Scholar databases only for articles written in the English language. Based on the currently published literature, it was observed that a low-calorie and low-protein diet with high contents of fiber, polyunsaturated fatty acids, vitamins, minerals and polyphenols contain sufficient potential macronutrients and micronutrients to regulate the activity of the overall disease by modulating the inflammation and immune functions of SLE.
Fulltext Editorial: Autoimmunity and cardiovascular diseases

Khandker SS, Kotyla PJ, Musa KI, Islam MA

Front Cardiovasc Med, 2023;10:1249525.
PMID: 37534278 DOI: 10.3389/fcvm.2023.1249525
Fulltext Diagnostic Accuracy of Rapid Antigen Test Kits for Detecting SARS-CoV-2: A Systematic Review and Meta-Analysis of 17,171 Suspected COVID-19 Patients

Khandker SS, Nik Hashim NHH, Deris ZZ, Shueb RH, Islam MA

J Clin Med, 2021 Aug 08;10(16).
PMID: 34441789 DOI: 10.3390/jcm10163493

Early diagnosis is still as crucial as the initial stage of the COVID-19 pandemic. As RT-PCR sometimes is not feasible in developing nations or rural areas, health professionals may use a rapid antigen test (RAT) to lessen the load of diagnosis. However, the efficacy of RAT is yet to be investigated thoroughly. Hence, we tried to evaluate the overall performance of RAT in SARS-CoV-2 diagnosis. Based on our PROSPERO registered protocol (CRD42021231432), we searched online databases (i.e., PubMed, Google Scholar, Scopus, and Web of Science) and analysed overall pooled specificity and sensitivity of RAT along with study quality, publication bias, heterogeneity and more. The overall pooled specificity and sensitivity of RAT were detected as 99.4% (95% CI: 99.1-99.8; I2 = 90%) and 68.4% (95% CI: 60.8-75.9; I2 = 98%), respectively. In subgroup analyses, nasopharyngeal specimens and symptomatic patient's samples were more sensitive in RAT, while cycle threshold (Ct) values were found to have an inverse relationship with sensitivity. In the European and American populations, RAT showed better performance. Although the sensitivity of RAT is yet to be improved, it could still be an alternative in places with poor laboratory set up. Nevertheless, the negative samples of RAT can be re-tested using RT-PCR to reduce false negative results.
Alzheimer's Disease and Natural Products: Future Regimens Emerging from Nature

Islam MA, Khandker SS, Alam F, Khalil MI, Kamal MA, Gan SH

Curr Top Med Chem, 2017;17(12):1408-1428.
PMID: 28049401 DOI: 10.2174/1568026617666170103163054

Alzheimer's disease (AD), which largely affects the elderly, has become a global burden. Patients with AD have both short- and long-term memory impairments. The neuronal loss in AD occurs due to abnormally folded amyloid beta proteins and aggregation of hyperphosphorylated tau proteins in the brain. Eventually, amyloid plaques and neurofibrillary tangles are formed, which subsequently disintegrate the neuronal transport system. There are several factors which are involved in AD pathogenesis, including oxidative stress, inflammation and the presence of metal ions. The modern therapies utilized for AD treatment have many adverse effects, driving the quest for more safe and effective medications. Many dietary components, including different types of fruits, vegetables, spices, and marine products as well as a Mediterranean diet, are a good source of antioxidants and have anti-inflammatory properties, with many showing substantial potential against AD pathogenesis. In this review, we discuss the potential of these foods for treating AD and opportunities for developing disease-targeted drugs from active compounds extracted from natural dietary products.
Genetic risk factors in thrombotic primary antiphospholipid syndrome: A systematic review with bioinformatic analyses

Islam MA, Khandker SS, Alam F, Kamal MA, Gan SH

Autoimmun Rev, 2018 Mar;17(3):226-243.
PMID: 29355608 DOI: 10.1016/j.autrev.2017.10.014

BACKGROUND: Antiphospholipid Syndrome (APS) is an autoimmune multifactorial disorder. Genetics is believed to play a contributory role in the pathogenesis of APS, especially in thrombosis development and pregnancy morbidity. In the last 20 years, extensive research on genetic contribution on APS indicates that APS is a polygenic disorder, where a number of genes are involved in the development of its clinical manifestations.

AIMS: The aim of this systematic review is to evaluate the genetic risk factors in thrombotic primary APS. Additionally, to assess the common molecular functions, biological processes, pathways, interrelations with the gene encoded proteins and RNA-Seq-derived expression patterns over different organs of the associated genes via bioinformatic analyses.

METHODS: Without restricting the year, a systematic search of English articles was conducted (up to 4th September 2017) using Web of Science, PubMed, Scopus, ScienceDirect and Google Scholar databases. Eligible studies were selected based on the inclusion criteria. Two researchers independently extracted the data from the included studies. Quality assessment of the included studies was carried out using a modified New-Castle Ottawa scale (NOS).

RESULTS: From an initial search result of 2673 articles, 22 studies were included (1268 primary APS patients and 1649 healthy controls). Twenty-two genes were identified in which 16 were significantly associated with thrombosis in primary APS whereas six genes showed no significant association with thrombosis. Based on the NOS, 14 studies were of high quality while 6 were low quality studies. From the bioinformatic analyses, thrombin-activated receptor activity (q = 6.77 × 10-7), blood coagulation (q = 2.63 × 10-15), formation of fibrin clot (q = 9.76 × 10-10) were the top hit for molecular function, biological process and pathway categories, respectively. With the highest confidence interaction score of 0.900, all of the thrombosis-associated gene encoded proteins of APS were found to be interconnected except for two. Based on the pathway analysis, cumulatively all the genes affect haemostasis [false discovery rate (FDR) = 1.01 × 10-8] and the immune system [FDR = 9.93 × 10-2]. Gene expression analysis from RNA-Seq data revealed that almost all the genes were expressed in 32 different tissues in the human body.

CONCLUSION: According to our systematic review, 16 genes contribute significantly in patients with thrombotic primary APS when compared with controls. Bioinformatic analyses of these genes revealed their molecular interconnectivity in protein levels largely by affecting blood coagulation and immune system. These genes are expressed in 32 different organs and may pose higher risk of developing thrombosis anywhere in the body of primary APS patients.
Fulltext Prevalence of antiphospholipid antibodies in Behçet's disease: A systematic review and meta-analysis

Islam MA, Alam SS, Kundu S, Prodhan AHMSU, Khandker SS, Reshetnyak T, et al.

PLoS One, 2020;15(1):e0227836.
PMID: 31929597 DOI: 10.1371/journal.pone.0227836

Behçet's disease (BD) is a multifactorial systemic inflammatory disease of unknown aetiology characterised by several clinical manifestations including vascular involvements (i.e., both arterial and venous thrombosis). Antiphospholipid antibodies (aPLs)-including anticardiolipin (aCL), anti-β2-glycoprotein I (β2-GPI) antibodies and lupus anticoagulant (LA) are detected in systemic autoimmune diseases which contribute to thrombosis. The aim of this systematic review and meta-analysis was to evaluate the prevalence of aPLs in patients with BD as compared to controls. A protocol was registered in PROSPERO (Registration No. CRD42018088125) and a systematic literature search was conducted through PubMed, Web of Science, Embase, Scopus and ScienceDirect databases. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using random-effects model. Quality assessment was carried out by using the modified 9-star Newcastle-Ottawa Scale (NOS). Publication bias was evaluated via visualisation of contour- enhanced and trim and fill funnel plots along with Begg's and Egger's tests. We included ten case-control studies (a total of 999 participants from 380 BD patients and 619 controls) based on the inclusion criteria. The prevalence of aCL (OR: 12.10, 95% CI: 5.15-28.41, p<0.00001) and anti-β2-GPI antibodies (OR: 23.57, 95% CI: 1.31-423.63, p = 0.03) were statistically significant, however, the prevalence of LA was not significant (OR: 13.77, 95% CI: 0.65-293.59, p = 0.09). The results remained statistically significant from different sensitivity analyses which represented the robustness of this meta-analysis. According to the NOS, 50.0% of the studies were considered as of high methodological quality (low risk of bias). No significant publication bias was detected from contour-enhanced and trim and fill funnel plots or Begg's and Egger's tests. This meta-analysis established that there is a significantly high prevalence of aPLs (i.e., aCL and anti-β2-GPI antibodies) in patients with BD when compared to controls.
Breast Cancer Management in the Era of Covid-19; Key Issues, Contemporary Strategies, and Future Implications

Prodhan AHMSU, Islam DZ, Khandker SS, Jamiruddin MR, Abdullah A, Godman B, et al.

Breast Cancer (Dove Med Press), 2023;15:51-89.
PMID: 36733464 DOI: 10.2147/BCTT.S390296

During the COVID-19 pandemic, several priority diseases were not getting sufficient attention. Whilst breast cancer is a fatal disease affecting millions worldwide, identification and management of these patients did not initially attract critical attention to minimize the impact of lockdown, post-lockdown, and other measures. Breast cancer patients' conditions may not remain stable without proper care, worsening their prognosis. Proper care includes the timely instigation of surgery, systemic therapy, and psychological support. This includes low-and middle-income countries where there are already concerns with available personnel and medicines to adequately identify and treat these patients. Consequently, there was a need to summarize the current scenario regarding managing breast cancer care during COVID-19 across all countries, including any guidelines developed. We systematically searched three scientific databases and found 76 eligible articles covering the medical strategies of high-income countries versus LMICs. Typically, diagnostic facilities in hospitals were affected at the beginning of the pandemic following the lockdown and other measures. This resulted in more advanced-stage cancers being detected at initial presentation across countries, negatively impacting patient outcomes. Other than increased telemedicine, instigating neo-adjuvant endocrine therapy more often, reducing non-essential visits, and increasing the application of neo-adjuvant chemotherapy to meet the challenges, encouragingly, there was no other significant difference among patients in high-income versus LMICs. Numerous guidelines regarding patient management evolved during the pandemic to address the challenges posed by lockdowns and other measures, which were subsequently adopted by various high-income countries and LMICs to improve patient care. The psychological impact of COVID-19 and associated lockdown measures, especially during the peak of COVID-19 waves, and the subsequent effect on the patient's mental health must also be considered in this high-priority group. We will continue to monitor the situation to provide direction in future pandemics.
Fulltext A Systematic Review on COVID-19 Vaccine Strategies, Their Effectiveness, and Issues

Khandker SS, Godman B, Jawad MI, Meghla BA, Tisha TA, Khondoker MU, et al.

Vaccines (Basel), 2021 Nov 24;9(12).
PMID: 34960133 DOI: 10.3390/vaccines9121387

COVID-19 vaccines are indispensable, with the number of cases and mortality still rising, and currently no medicines are routinely available for reducing morbidity and mortality, apart from dexamethasone, although others are being trialed and launched. To date, only a limited number of vaccines have been given emergency use authorization by the US Food and Drug Administration and the European Medicines Agency. There is a need to systematically review the existing vaccine candidates and investigate their safety, efficacy, immunogenicity, unwanted events, and limitations. The review was undertaken by searching online databases, i.e., Google Scholar, PubMed, and ScienceDirect, with finally 59 studies selected. Our findings showed several types of vaccine candidates with different strategies against SARS-CoV-2, including inactivated, mRNA-based, recombinant, and nanoparticle-based vaccines, are being developed and launched. We have compared these vaccines in terms of their efficacy, side effects, and seroconversion based on data reported in the literature. We found mRNA vaccines appeared to have better efficacy, and inactivated ones had fewer side effects and similar seroconversion in all types of vaccines. Overall, global variant surveillance and systematic tweaking of vaccines, coupled with the evaluation and administering vaccines with the same or different technology in successive doses along with homologous and heterologous prime-booster strategy, have become essential to impede the pandemic. Their effectiveness appreciably outweighs any concerns with any adverse events.
Fulltext AuNP Coupled Rapid Flow-Through Dot-Blot Immuno-Assay for Enhanced Detection of SARS-CoV-2 Specific Nucleocapsid and Receptor Binding Domain IgG

Sil BK, Jamiruddin MR, Haq MA, Khondoker MU, Jahan N, Khandker SS, et al.

Int J Nanomedicine, 2021;16:4739-4753.
PMID: 34267520 DOI: 10.2147/IJN.S313140

BACKGROUND: Serological tests detecting severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) are widely used in seroprevalence studies and evaluating the efficacy of the vaccination program. Some of the widely used serological testing techniques are enzyme-linked immune-sorbent assay (ELISA), chemiluminescence immunoassay (CLIA), and lateral flow immunoassay (LFIA). However, these tests are plagued with low sensitivity or specificity, time-consuming, labor-intensive, and expensive. We developed a serological test implementing flow-through dot-blot assay (FT-DBA) for SARS-CoV-2 specific IgG detection, which provides enhanced sensitivity and specificity while being quick to perform and easy to use.
METHODS: SARS-CoV-2 antigens were immobilized on nitrocellulose membrane to capture human IgG, which was then detected with anti-human IgG conjugated gold nanoparticle (hIgG-AuNP). A total of 181 samples were analyzed in-house. Within which 35 were further evaluated in US FDA-approved CLIA Elecsys SARS-CoV-2 assay. The positive panel consisted of RT-qPCR positive samples from patients with both <14 days and >14 days from the onset of clinical symptoms. The negative panel contained samples collected from the pre-pandemic era dengue patients and healthy donors during the pandemic. Moreover, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of FT-DBA were evaluated against RT-qPCR positive sera. However, the overall efficacies were assessed with sera that seroconverted against either nucleocapsid (NCP) or receptor-binding domain (RBD).
RESULTS: In-house ELISA selected a total of 81 true seropositive and 100 seronegative samples. The sensitivity of samples with <14 days using FT-DBA was 94.7%, increasing to 100% for samples >14 days. The overall detection sensitivity and specificity were 98.8% and 98%, respectively, whereas the overall PPV and NPV were 99.6% and 99%. Moreover, comparative analysis between in-house ELISA assays and FT-DBA revealed clinical agreement of Cohen's Kappa value of 0.944. The FT-DBA showed sensitivity and specificity of 100% when compared with commercial CLIA kits.
CONCLUSION: The assay can confirm past SARS-CoV-2 infection with high accuracy within 2 minutes compared to commercial CLIA or in-house ELISA. It can help track SARS-CoV-2 disease progression, population screening, and vaccination response. The ease of use of the assay without requiring any instruments while being semi-quantitative provides the avenue of its implementation in remote areas around the globe, where conventional serodiagnosis is not feasible.
Fulltext Longitudinal Antibody Dynamics Against Structural Proteins of SARS-CoV-2 in Three COVID-19 Patients Shows Concurrent Development of IgA, IgM, and IgG

Jamiruddin MR, Haq MA, Tomizawa K, Kobatake E, Mie M, Ahmed S, et al.

J Inflamm Res, 2021;14:2497-2506.
PMID: 34163208 DOI: 10.2147/JIR.S313188

BACKGROUND: Dynamics and persistence of neutralizing and non-neutralizing antibodies can give us the knowledge required for serodiagnosis, disease management, and successful vaccine design and development. The disappearance of antibodies, absence of humoral immunity activation, and sporadic reinfection cases emphasize the importance of longitudinal antibody dynamics against variable structural antigens.
METHODS: In this study, twenty-five healthy subjects working in a SARS-COV-2 serodiagnostic assay development project were enrolled, and their sign and symptoms were followed up to six months. Three subjects showed COVID-19-like symptoms, and three subjects' antibody dynamics were followed over 120 days by analyzing 516 samples. We have developed 12 different types of in-house ELISAs to observe the kinetics of IgG, IgM, and IgA against four SARS-CoV-2 proteins, namely nucleocapsid, RBD, S1, and whole spike (S1+S2). For the development of these assays, 30-104 pre-pandemic samples were taken as negative controls and 83 RT-qPCR positive samples as positive ones.
RESULTS: All three subjects presented COVID-19-like symptoms twice, with mild symptoms in the first episode were severe in the second, and RT-qPCR confirmed the latter. The initial episode did not culminate with any significant antibody development, while a multifold increase in IgG antibodies characterized the second episode. Interestingly, IgG antibody development concurrent with IgM and IgA and persisted, whereas the latter two weans off rather quickly if appeared.
CONCLUSION: Antibody kinetics observed in this study can provide a pathway to the successful development of sero-diagnostics and epidemiologists to predict the fate of vaccination currently in place.
Fulltext COVID-19 Pandemic: Review of Contemporary and Forthcoming Detection Tools

Oishee MJ, Ali T, Jahan N, Khandker SS, Haq MA, Khondoker MU, et al.

Infect Drug Resist, 2021;14:1049-1082.
PMID: 33762831 DOI: 10.2147/IDR.S289629

Recent severe acute respiratory syndrome 2 (SARS-CoV-2) known as COVID-19, presents a deadly challenge to the global healthcare system of developing and developed countries, exposing the limitations of health facilities preparedness for emerging infectious disease pandemic. Opportune detection, confinement, and early treatment of infected cases present the first step in combating COVID-19. In this review, we elaborate on various COVID-19 diagnostic tools that are available or under investigation. Consequently, cell culture, followed by an indirect fluorescent antibody, is one of the most accurate methods for detecting SARS-CoV-2 infection. However, restrictions imposed by the regulatory authorities prevented its general use and implementation. Diagnosis via radiologic imaging and reverse transcriptase PCR assay is frequently employed, considered as standard procedures, whereas isothermal amplification methods are currently on the verge of clinical introduction. Notably, techniques such as CRISPR-Cas and microfluidics have added new dimensions to the SARS-CoV-2 diagnosis. Furthermore, commonly used immunoassays such as enzyme-linked immunosorbent assay (ELISA), lateral flow immunoassay (LFIA), neutralization assay, and the chemiluminescent assay can also be used for early detection and surveillance of SARS-CoV-2 infection. Finally, advancement in the next generation sequencing (NGS) and metagenomic analysis are smoothing the viral detection further in this global challenge.
Fulltext Detection of SARS-CoV-2 by antigen ELISA test is highly swayed by viral load and sample storage condition

Adnan N, Khandker SS, Haq A, Chaity MA, Khalek A, Nazim AQ, et al.

Expert Rev Anti Infect Ther, 2021 Sep 11.
PMID: 34477019 DOI: 10.1080/14787210.2021.1976144

BACKGROUND: Rapid increase in COVID-19 suspected cases has rendered disease diagnosis challenging, mainly depending upon RT-qPCR. Reliable, rapid, and cost-effective diagnostic assays that complement RT-qPCR should be introduced after thoroughly evaluating their performance upon various disease phases, viral load, and sample storage conditions.
OBJECTIVE: We investigated the correlation of cycle threshold (Ct) value, which implies the viral load and infection phase, and the storage condition of the clinical specimen with the diagnosis of SARS-CoV-2 through our newly developed in-house rapid enzyme-linked immunosorbent assay (ELISA) system.
METHOD: Naso-oropharyngeal samples of 339 COVID-19 suspected cases were collected and evaluated through RT-qPCR that were stored up to 30 days in different conditions (i.e. -80°C, -20°C and initially at 4°C followed by -80°C). The clinical specimens were evaluated with our in-house ELISA system after finalizing the assay method through checkerboard assay and minimizing the signal/noise ratio.
RESULT: The ELISA system showed the highest sensitivity (92.9%) for samples with Ct ≤30 and preserving at -80°C temperature. The sensitivity reduced proportionally with increasing Ct value and preserving temperature. However, the specificity ranged between 98.3% and 100%.
CONCLUSION: The results indicate the necessity of early infection phase diagnosis and lower temperature preservation of samples to perform rapid antigen ELISA tests.
Fulltext Antibody response to the first dose of AZD1222 vaccine in COVID-19 convalescent and uninfected individuals in Bangladesh

Jamiruddin R, Haq A, Khondoker MU, Ali T, Ahmed F, Khandker SS, et al.

Expert Rev Vaccines, 2021 12;20(12):1651-1660.
PMID: 34503369 DOI: 10.1080/14760584.2021.1977630

BACKGROUND: Vaccination with the Oxford-AstraZeneca COVID-19 vaccine (AZD1222) initially started in the UK and quickly implemented around the Globe, including Bangladesh. Up to date, more than nine million doses administrated to the Bangladeshi public.
METHOD: Herein, we studied the antibody response to the first dose of AZD1222 in 86 Bangladeshi individuals using in-house ELISA kits. Study subjects were categorized into two groups, convalescent and uninfected, based on prior infection history and SARS-CoV-2 nucleocapsid-IgG profiles.
RESULTS: All the convalescent individuals presented elevated spike-1-IgG compared to 90% of uninfected ones after the first dose. Day >28 post-vaccination, the convalescent group showed six times higher antibody titer than the uninfected ones. The most elevated antibody titers for the former and later group were found at Day 14 and Days >28 post-vaccination, respectively. The spike-1-IgA titer showed a similar pattern as spike-1-IgG, although in a low-titer. In contrast, the IgM titer did not show any significant change in either group.
CONCLUSION: High antibody titer in the convalescent group, signify the importance of the first dose among the uninfected group. This study advocates the integration of antibody tests in vaccination programs in the healthcare system for maximizing benefit.

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