Development and Validation of a Three-Parameter Scoring System for Monitoring HIV/AIDS Patients in Low-Resource Settings Using Hematological Parameters.

Objective: This study aimed to test the validity of a composite score using complete blood count (CBC) for monitoring HIV patients receiving antiretroviral therapy (ART) in the absence of viral load and CD4 count. Methods: This retrospective cohort study analyzed the laboratory data of 82 HIV patients who had pre- and post-treatment viral load, CD4 count, and CBC data. Pre- and post-treatment data were pooled to analyze the correlation of CBC parameters with Polymerase Chain Reaction (PCR) ranks and their performance in indicating a CD4 count<200 cells/mm3 using the Operating Characteristics Curve (ROC), with the determination of cutoffs. A score combining the significant parameters was tested to predict a CD4 count of <200. Results: Total lymphocyte count (TLC), percentage (TLP), and hemoglobin concentration (Hb) were the most significant parameters, showing negative correlations with PCR (Spearman's Rho = -0.357 to -0.242). The risk of acquired immunodeficiency syndrome (AIDS) was independently associated with TLC<1345 cells/mm3 (OR=2.92), TLP<29.07% (OR=3.53), and Hb<10.55 mg/dL (OR=3.60). A combined score of 2-3 indicated a CD4 count<200 with an odds ratio of 8.3-86.7. Conclusion: The proposed 3-parameter score combining the use of TLC, TLP, and Hb, is an affordable and practical approach that may have clinical utility in monitoring HIV patients receiving ART in low-resource settings.

Anti-Nuclear Antibodies Patterns in Patients With Systemic Lupus Erythematosus and Their Correlation With Other Diagnostic Immunological Parameters.

Background: Antinuclear antibodies (ANA) are major immunodiagnostic tools in systemic lupus erythematosus (SLE); however, their clinical and pathogenic roles are not yet elucidated and are a subject of controversy. Objectives: The aim of the study is to explore the pathogenic significance of ANA patterns among SLE patients, by analyzing their association with ANA titers, complement levels and other pathogenic immune markers, namely, anti-double-stranded DNA (anti-dsDNA), complements C3 and C4, rheumatoid factor (RF), anticardiolipin antibodies IgG (ACL IgG) and IgM (ACL IgM), Beta-2 Glycoprotein 1 Antibodies (ß2-GP) IgG (ß2-IgM) and IgM (ß2-IgM), and lupus anticoagulant (LA). Method: A comparative cross-sectional study was conducted among 495 SLE patients, who were diagnosed and classified by consultant rheumatologists according to the new European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) 2019 criteria. SLE immunodiagnostic profiles were analyzed including the following parameters: ANA antibody titers and staining patterns, anti-dsDNA, C3 and C4 levels, aCL, and anti-ß2-GP and LA. Result: The most frequently observed ANA patterns were the speckled (52.1%) and homogeneous (35.2%) patterns, while other patterns were rare representing less than 7% of the patients each. ANA titers were highest in patients with mixed pattern followed by the speckled pattern. Of all the investigated patterns, the peripheral pattern showed the most pathogenic immune profile, namely, highest levels of anti-dsDNA, lowest levels of C4, and highest levels of aCL and ß2-GP IgG and IgM. Conclusion: This retrospective study showed that speckled followed by homogeneous ANA patterns were predominant accounting for 52.1 and 35.2% of the patients. The ANA pattern showed several associations with other immune markers that are documented to have significant clinical implications in SLE. Peripheral, mixed, and speckled patterns were associated with higher profiles of immune markers indicative of a potential prognostic value of these patterns in SLE.

Monitoring Specific IgM and IgG Production Among Severe COVID-19 Patients Using Qualitative and Quantitative Immunodiagnostic Assays: A Retrospective Cohort Study.

The purpose of this study is to monitor specific anti-severe acute respiratory syndrome coronavirus 2 (anti-SARS-CoV-2) IgG and IgM antibody production in patients with severe forms of coronavirus disease 2019 (COVID-19) using various commercially available quantitative and qualitative tests. The sera of 23 confirmed COVID-19 patients were processed for anti-SARS-CoV-2 IgG and IgM detection. Three different immunoassays, viz. Abbott Architect® SARS-CoV-2 IgG assay, and two quantitative tests, ANSH® SARS-CoV-2 and AESKULISA® SARS-CoV-2 Nucleocapsid Protein (NP), were performed and the results pooled, from diagnosis to serum collection. Seroconversion rates were computed for all 3 assays, and possible correlations were tested using the Pearson correlation coefficient and Cohen's kappa coefficient. Overall, 70 combinations of qualitative and quantitative IgG and IgM results were pooled and analyzed. In the early phase (0-4 days after diagnosis), in all tests, IgG seroconversion rates were 43%-61%, and increased in all tests gradually to 100% after 15 days. The Pearson correlation coefficient showed a strong positive relationship between the qualitative IgG test results and both quantitative IgG tests. IgM detection was inconsistent, with maximal concentrations and seroconversion rates between 10-15 days after diagnosis and slight-to-fair agreement between the two quantitative immunoassays. There was no significant association between mortality with IgG or IgM seroconversion or concentrations. Patients with severe COVID-19 develop an early, robust anti-SARS-CoV-2 specific humoral immune response involving IgG immunoglobulins. Further comparative studies are warranted to analyze the value of serological testing in predicting the severity of COVID-19 and detecting prior exposure.

Inappropriate practice in tumor marker requests at a university hospital in Western Saudi Arabia: A 3-year retrospective study.

OBJECTIVES: This study assessed the level of appropriateness of tumor marker requests in a teaching hospital and estimated the financial cost associated with inappropriate use. METHODS: A retrospective review of patients' electronic records was conducted over a 3-year period (2015-2017) for tumor marker requests, including carcinoembryonic antigen, alpha-fetoprotein, cancer antigen (CA)15-3, CA125, CA19-9, and total and free prostate-specific antigen (PSA and fPSA), along with the associated clinical data that motivated the requests. Inappropriate use was defined as tumor marker requests without any relevant clinical picture. Costs due to inappropriate tumor marker requests were estimated based on the unit costs applied in the institution. RESULTS: A total of 7128 patients had at least one tumor marker request between 2015 and 2017. The clinical picture that motivated tumor marker requests was absent in 71.5%, while 12.9% of the requests were associated with a malignancy. The most frequent prescribing pattern was total prostate-specific antigen alone (2128; 29.9%), followed by alpha-fetoprotein alone (1185; 16.6%), and carcinoembryonic antigen alone (506; 7.1%). Year-over-year analysis revealed an increasing tendency in requesting carcinoembryonic antigen and CA15-3. The rate of inappropriate use varied by tumor marker and ranged between 56.4% for fPSA and 86.8% for total prostate-specific antigen. The overall costs due to inappropriate tumor marker requests were estimated at $2,785,493 over the 3 years, representing an average of $0.93 million per year. CONCLUSION: Inappropriate use of tumor marker requests is a major issue regarding its high prevalence and the considerable associated costs. The role of laboratories in the management of tumor marker requests should be emphasized.

Deamidated gliadin peptide and tissue transglutaminase antibodies in children with coeliac disease: A correlation study.

BACKGROUND AND STUDY AIMS: Serological tests for coeliac disease (CD) are important in the clinical diagnosis and monitoring of response to a gluten free diet (GFD). The tests differ in their sensitivity, specificity, and diagnostic accuracy. In this study, tissue transglutaminase (IgA) (tTG-IgA) antibody was compared with the deamidated gliadin peptide (DGP), of both IgG (DGP-IgG) and IgA (DGP-IgA) types, in patients with CD. PATIENTS AND METHODS: This cross-sectional study was conducted over a period of 2 years, between 2016 and 2018, at King Abdulaziz University Hospital in children 18 years of age or younger with biopsy-proven CD. Patients' sera were tested for DGP-IgA, DGP-IgG, and tTG-IgA antibodies using enzyme-linked immunosorbent assay (ELISA). A Pearson correlation coefficient and Cohen's kappa coefficient were performed to analyse the serological tests. RESULTS: The study included 26 patients with CD, with a median age of 15 years (range, 5-18 years). Seventeen patients (65.4%) were males. The median disease duration was 5 years (range, 3-14 years). Fifteen patients (57.7%) reported good adherence to a GFD. The patients' serological tests showed a mean ± SD tTG-IgA titer of 149.8 ± 75 u/ml, a mean DGP-IgG titer of 62.5 ± 36.5, and a mean DGP-IgA of 32 ± 23.3 µ/ml. We found a significant correlation between tTG-IgA and DGP-IgG (r = 0.69, P < 0.001), tTG-IgA and DGP-IgA (r = 0.67, P < 0.001), and DGP-IgG and DGP-IgA (r = 0.83, P < 0.001). Cohen's kappa coefficient (k) showed substantial agreement between tTG-IgA and DGP-IgG (k = 0.71, P < 0.001) and DGP-IgG and DGP-IgA (k = 0.69, P < 0.001), but moderate agreement between tTG-IgA and DGP-IgA (k = 0.45, P = 0.006). CONCLUSION: We found a good correlation between tTG-IgA and DGP-IgG and tTG-IgA and DGP-IgA, and substantial agreement between tTG-IgA and DGP-IgG, but moderate agreement between tTG-IgA and DGP-IgA. These results indicate that DGP-IgG was comparable to tTG-IgA and may be useful as an alternative to tTG-IgA in the diagnosis and follow-up of patients with CD.

Saudi children with celiac disease: are they at risk of developing type-1 diabetes mellitus?

Objectives Patients with type-1 diabetes mellitus (T1DM) and celiac disease (CeD) share the same genetic susceptibility alleles. The diabetes-associated autoantibodies (DAA) may be detected in CeD patients. The aim of this study is to describe the prevalence of DAA in children with CeD. Methods This is a cross-sectional study of children with CeD. The CeD patients were divided into two groups; group 1 (n=23) included patients with isolated CeD and group 2 included patients with combined T1DM and CeD. The study was conducted at King Abdulaziz University Hospital (KAUH) in 2012-2014. DAA, including glutamic acid decarboxylase antibodies (GADA) and protein tyrosine phosphatase-2 antibodies (IA-2), were measured by enzyme-linked immunosorbent assay (ELISA) in both groups. Clinical, demographic, and laboratory data were collected from the patients' medical charts. Results DAA were determined in 23 patients in group-1 and 18 patients in group-2. Group-1 comprised 43.5% males and 56.5% females; the mean age was 15 ± 3.7 years (with a range of 5-18 years). The prevalence of GADA and IA-2 was 69.6 and 4%, respectively. Group-2 comprised 55.6% males and 44.4% females; the mean age was 15.1 ± 2.8 years (with a range of 7-18 years). The prevalence of GADA and IA-2 was 66.7 and 22.2%, respectively. No significant differences were found between both groups in the prevalence of GADA (p=1.0) or IA-2 (p=0.15). Conclusions Saudi children with CeD have higher prevalence of GADA than reported in a number of other Western studies. Long-term follow-up data is required before recommending routine screening for DAA.

Diagnostic Utility of Total IgE in Foods, Inhalant, and Multiple Allergies in Saudi Arabia.

Objective. To assess the diagnostic significance of total IgE in foods, inhalant, and multiple allergies. Methods. Retrospective review of the laboratory records of patients who presented with clinical suspicion of food or inhalant allergy between January 2013 and December 2014. Total IgE level was defined as positive for a value >195 kU/L; and diagnosis was confirmed by the detection of specific IgE (golden standard) for at least one food or inhalant allergen and at least two allergens in multiple allergies. Results. A total of 1893 (male ratio = 0.68, mean age = 39.0 ± 19.2 years) patients were included. Total IgE had comparable sensitivity (55.8% versus 59.6%) and specificity (83.9% versus 84.4%) in food versus inhalant allergy, respectively, but a superior PPV in inhalant allergy (79.1% versus 54.4%). ROC curve analysis showed a better diagnostic value in inhalant allergies (AUC = 0.817 (95% CI = 0.796-0.837) versus 0.770 (95% CI = 0.707-0.833)). In multiple allergies, total IgE had a relatively good sensitivity (78.6%), while negative IgE testing (<195 kU/L) predicted the absence of multiple allergies with 91.5% certitude. Conclusion. Total IgE assay is not efficient as a diagnostic test for foods, inhalant, or multiple allergies. The best strategy should refer to specific IgE testing guided by a comprehensive atopic history.

Co-infection assessment in HBV, HCV, and HIV patients in Western Saudi Arabia.

To estimate the prevalence of diagnosed and undiagnosed coinfections among HIV, HBV, and HCV infected patients. Retrospective analysis of laboratory records for HIV, HBV, and HCV patients presenting at the HIV outpatient clinic. Serological data including hepatitis B surface antigen (HBsAg), hepatitis B e-antigen (HBeAg), hepatitis B e-antibody (anti-HBe), antibodies to HIV and HCV, anti-toxoplasmosis IgG and IgM antibodies, and anti-syphilis antibodies (VDRL) were collected. We obtained data for 628 (218 HCV, 268 HBV, and 142 HIV) patients. Male-to-female ratios were 1:1 for HCV, 3:4 for HBV, and 5:3 for HIV. Age means (SD) were 54.24 (16.40), 44.53 (18.83), and 40.39 (15.92) years for HCV, HBV, and HIV, respectively. In HIV group, the prevalence of HBV and HCV coinfections was 8.5% and 2.8%, respectively. In HBV group, the prevalence of HCV and HIV coinfections was 1.1% and 1.5%, respectively. In HCV group, HIV or HBV coinfections occurred at the same frequency (1.4%). An absence of screening for coinfections was detected in 7.0-48.5% patients as per the group and the infectious agent; which represents an estimated proportion of 20 out of 1,000 patients with an undiagnosed coinfection. Despite a relatively low prevalence of coinfections, a significant proportion of cases remain undiagnosed because of a lack of systematic screening. J. Med. Virol. 88:1545-1551, 2016. © 2016 Wiley Periodicals, Inc.

Immunodiagnostic significance of anti-RA33 autoantibodies in Saudi patients with rheumatoid arthritis.

UNLABELLED: The primary objective of this study was to evaluate and compare the immunodiagnostic significance and utility of anti-RA33 with anti-CCP, RF, and CRP in Saudi patients with rheumatoid arthritis. METHODS: This was a prospective controlled clinical study conducted at King Abdul Aziz University Tertiary Medical Centre. The sera of 41 RA patients, 31 non-RA patients, and 29 healthy controls were collected. Anti-RA33 and anti-CCP were measured using commercially available ELISA principle kits. RF and CRP were measured using nephelometry. RESULTS: Anti-RA33 antibodies had the lowest positive and negative predictive values and showed a sensitivity of 7.32% with 95.12% specificity. Of the other three markers (including anti-CCP antibodies, CRP, and RF), only anti-CCP showed specificity of 90.46% with sensitivity of 63.41% compared to non-RA patients + healthy control. There was a significant correlation with rheumatoid factor positivity with anti-CCP. With respect to CRP, a notable correlation was seen only with anti-RA33. CONCLUSION: Compared to rheumatoid factor, anti-CCP antibodies, and C-reactive proteins, the anti-RA33 autoantibodies seem to be not representing as an important additional immunodiagnostic marker in Saudi patients with established RA. RA33 may have more interest in early RA or less severe RA and other systemic connective tissue disorders.

Serum Interleukin-33 level in Saudi children with inflammatory bowel disease.

Interleukin-33 (IL-33) is a cytokine that belongs to the interleukin-1 family and has been shown to be associated with mucosal inflammation. The aim of this study was to determine the serum level of IL-33 in children with ulcerative colitis (UC) and Crohn's disease (CD) and to correlate the level with the disease progression. In this cross sectional prospective study, we enrolled 50 children with IBD from KAUH, Jeddah, Saudi Arabia and 34 healthy control subjects between June 2012 and December 2012. Serum IL-33 was assessed by ELISA and CRP by immunonephelometric assay. Results from our study showed 32 CD and 18 UC patients included. The median age was 13.5 years for CD patients, 11.9 years for UC patients and 11.2 years for controls. Females constituted 53%, 66.7% and 59% of CD, UC and control subjects respectively. The median serum IL-33 in UC patients of 55.5 pg/mL was significantly higher than the median IL-33 level of 41 pg/mL in the healthy control (P=0.04) but no significant difference was found between the median IL-33 level in the sera of CD and the control group (P=0.7). A higher median IL-33 level was also found in active disease (P=0.03). In our cohort, the serum level of IL-33 was positively correlated with hs-CRP (r=0.48, P < 0.001). To conclude, our results support that serum IL-33 level is increased in children with UC as compared with control. Serum level is correlated with the disease activity; therefore it could be used as a potential biomarker for monitoring the severity of the disease in children with UC.

Serological markers of inflammatory bowel disease in children from the Western region of Saudi Arabia.

BACKGROUND AND STUDY AIMS: Serological markers including peri-nuclear anti-neutrophil cytoplasmic antibodies (pANCA) and anti-Saccharomyces cerevisiae antibodies (ASCA) have been reported in relation to inflammatory bowel disease (IBD). The aim of this study was to ascertain the prevalence and diagnostic accuracy of pANCA and ASCA antibodies in Saudi children with IBD. PATIENTS AND METHODS: A retrospective case-control study of children with IBD seen at King Abdulaziz University Hospital, Jeddah, between September 2002 and February 2012. RESULTS: The study included 131 patients with IBD (86 Crohn's disease (CD) and 45 ulcerative colitis (UC)) and 67 non-IBD control subjects. Females comprised 51% of CD, 60% of UC and 52% of non-IBD controls. The mean age was 10.7±5.2years for CD, 8.9±5years for UC, and 11.2±6.8years for the non-IBD controls. Positive ASCA-IgA and ASCA-IgG were detected in 35.8% and 35% of CD patients and in 5.8% and 3.7% of the non-IBD controls, respectively. The pANCA was detected in 28.9% of UC patients and in none of the non-IBD controls. The pANCA recognised the myeloperoxidase (MPO) antibody in 36.4% of the patients with UC. No significant difference in the frequency of pANCA between extensive disease and disease limited to the rectosigmoid colon (p=0.48), and no significant difference in the ASCAs antibodies in patients with or without involvement of the terminal ileum (p=0.81). CONCLUSION: The prevalence of ASCA and pANCA antibodies was low in Saudi children with IBD. Therefore, it may not be useful as a screening tool for IBD but it may be employed to aid the diagnosis in clinically suspected cases.

Long-term efficacy of the hepatitis B vaccine in a high-risk group.

Chronic infection with hepatitis B virus (HBV) is a global health problem. In an attempt to control infection, worldwide HBV vaccination programs have been established. Saudi Arabia, an endemic area for HBV infection, established an HBV immunization program in 1989. This cross-sectional study evaluates the long-term protection of HBV vaccination 14-24 years after primary immunization in a high-risk group (clinical year medical students) at King Abdulaziz University Hospital in Jeddah, Saudi Arabia. All participants had complete HBV immunization at birth or in early childhood. Hepatitis B surface antibody (anti-HBs) levels were obtained. An anti-HBs titer of <10 mIU/ml indicated no protection, while a titer of >10 mIU/ml was considered to represent protective immune status. A total of 238 students were included; they were predominantly females (n = 182, 76.5%). Mean age was 22.2 ± 1.1 years. Duration since primary vaccination was 19.8 ± 2.3 years. Female students were more likely to maintain long-term protection compared to males (62.1% and 58.8%, respectively). Anti-HBs levels were significantly low in many students after primary immunization. Testing medical students for anti-HBs levels may be warranted as they represent a high-risk population. The higher rate of vaccine failure in males than females requires further investigation as it may explain the higher prevalence of HBV in the male population.

Pediatric inflammatory bowel disease with cytoplasmic staining of antineutrophil cytoplasmic antibodies.

BACKGROUND: It is unusual for the antineutrophil cytoplasmic antibody with cytoplasmic pattern (cANCA) to present in patients with inflammatory bowel disease (IBD) without vasculitis. The purpose of this study was to describe the occurrence and characteristics of pediatrics IBD with cANCA. METHODS: A retrospective review of pediatric IBD associated with cANCA serology in patients from King Abdulaziz University Hospital, Saudi Arabia, between September 2002 and February 2012. RESULTS: Out of 131 patients with IBD screened for cANCAs, cANCA was positive in 7 (5.3%) patients of whom 4 had ulcerative colitis and 3 had Crohn's disease. The median age was 8.8 years (2-14.8 years). Six (86%) were males. Of the 7 patients, 5 (71%) were Saudi Arabians and 2 were of Indian ethnicity. The most common symptoms were diarrhea, abdominal pain, weight loss, and rectal bleeding. None had family history or clinical features suggestive of vasculitis involving renal and respiratory systems. No difference in the disease location or severity was observed between cANCA positive and cANCA negative patients apart from male preponderance in cANCA positive patients. CONCLUSION: The occurrence of cANCA in pediatric IBD is rare. Apart from male preponderance, there were no peculiar characteristics for the cANCA positive patients.

Prevalence of celiac disease in children with type 1 diabetes mellitus screened by anti-tissue transglutaminase antibody from Western Saudi Arabia.

OBJECTIVE: To determine the prevalence of celiac disease (CD) in children and adolescents with type 1 diabetes mellitus (T1DM) using anti-tissue transglutaminase (anti-tTG) antibodies. METHODS: A retrospective hospital record-based study of all children and adolescents with T1DM who were screened for CD was conducted at the Pediatric Diabetes Clinic of King Abdulaziz University Hospital, Jeddah, Kingdom of Saudi Arabia (KSA) between October 2002 and June 2011. RESULTS: A total of 430 children with T1DM were screened by anti-tTG antibody. The median age at screening was 10.7 years (range; 1.1-18). The study cohort included 232 (54%) Saudi patients, and females constituted 58.8% of the total number. Anti-tTG antibody screening was positive in 91 (21.2%) patients. Forty-eight (11.2%) out of 430 children screened had biopsy-proven CD. Forty-two patients with CD (87.5%) were asymptomatic. Patients with CD had less weight for age (p=0.007), and height for age (p=0.03) z-scores than non-CD patients. They showed more association with anemia (p<0.001), low albumin level (p<0.001), and autoimmune thyroid disease (p=0.002). There was no difference in the mean glycosylated hemoglobin level (p=0.38), or insulin requirements (p=0.74) between the 2 groups. CONCLUSION: The prevalence of CD in patients with T1DM from the Western region of KSA is considered among the highest reported. Therefore, routine screening through proper serological testing is recommended.

Serum concentrations of interleukin-1 alpha, interleukin-6 and tumor necrosis factor-alpha in neonatal sepsis and meningitis.

OBJECTIVE: To investigate whether serum levels of interleukin-1alpha (IL-1alpha), IL-6, tumor necrosis factor alpha (TNF-alpha), C-reactive protein (CRP) are useful in the diagnosis of neonatal sepsis and meningitis and differentiate them. METHODS: Blood samples were collected from 35 full term neonates with suspected infection who admitted to the Neonatology Unit, Pediatric Department, King Abdul-Aziz University Hospital, Jeddah, Saudi Arabia during January 2002 - June 2003. On the basis of laboratory and bacteriological results, newborns were classified into: sepsis (n = 28), meningitis (n = 7), and healthy controls (n = 16). Sepsis groups were further subdivided according to culture results into: group 1 = proven sepsis (n = 6), group 2 = clinical sepsis (n = 14), and group 3 = possible-infected (n = 8). Serum levels of IL-1alpha, IL-6, TNF-alpha were measured using Enzyme-Linked Immunosorbent Assay while CRP by nephelometer. RESULTS: In sepsis and meningitis patients, serum levels of CRP (p < 0.01, p < 0.05,) and IL-1alpha (p < 0.001, p < 0.05) were elevated than controls. C-reactive protein levels elevated in proven sepsis (p < 0.001) and IL-1alpha elevated in all subgroups of sepsis (groups 1, 2, 3) compared with (p < 0.05, p < 0.001, p < 0.01) controls. Interleukin-6, TNF-alpha showed no significant differences between studied groups. In sepsis and meningitis, IL-1alpha had a highest sensitivity (89%, 86%), and negative predictive values (89% and 93%). CONCLUSION: Interleukin-1alpha and CRP increased in neonatal sepsis and meningitis, but cannot differentiate between them. Interleukin-1alpha had a highest sensitivity in prediction of neonatal infection and its assessment may improve accuracy of diagnosis.