Preclinical Serological Signatures are Associated With Complicated Crohn's Disease Phenotype at Diagnosis.

BACKGROUND: At diagnosis, up to one-third of patients with Crohn's disease (CD) have a complicated phenotype with stricturing (B2) or penetrating (B3) behavior or require early surgery. We evaluated protein biomarkers and antimicrobial antibodies in serum archived years before CD diagnosis to assess whether complicated diagnoses were associated with a specific serological signature. METHODS: Prediagnosis serum was obtained from 201 patients with CD and 201 healthy controls. Samples were evaluated with a comprehensive panel of 1129 proteomic markers (SomaLogic) and antimicrobial antibodies. CD diagnosis and complications were defined by the International Classification of Diseases-Ninth Revision and Current Procedural Terminology codes. Cox regression models were utilized to assess the association between markers and the subsequent risk of being diagnosed with complicated CD. In addition, biological pathway and network analyses were performed. RESULTS: Forty-seven CD subjects (24%) had a B2 (n = 36) or B3 (n = 9) phenotype or CD-related surgery (n = 2) at diagnosis. Subjects presenting with complicated CD at diagnosis had higher levels of antimicrobial antibodies six years before diagnosis as compared with those diagnosed with noncomplicated CD. Twenty-two protein biomarkers (reflecting inflammatory, fibrosis, and tissue protection markers) were found to be associated with complicated CD. Pathway analysis of the altered protein biomarkers identified higher activation of the innate immune system and complement or coagulation cascades up to six years before diagnosis in complicated CD. CONCLUSIONS: Proteins and antimicrobial antibodies associated with dysregulated innate immunity, excessive adaptive response to microbial antigens, and fibrosis precede and predict a complicated phenotype at the time of diagnosis in CD patients.

Mode of presentation and performance of serology assays for diagnosing celiac disease: A single-center study in the United Arab Emirates.

Objective: To characterize patients with celiac disease (CD), examines the clinical spectrum of CD, and evaluate the performance of serologic tests used for CD screening, in the United Arab Emirates (UAE). Methods: Medical charts of patients received at the Digestive Diseases Institute of Cleveland Clinic Abu Dhabi from January 2015 to December 2020 were reviewed. Patients who were screened for four serologic biomarkers (anti-tissue transglutaminase IgA [Anti-tTG-IgA], anti-tissue transglutaminase IgG [Anti-TtG-IgG], anti-deamidated gliadin peptide IgG [Anti-DGP-IgG], and anti-deamidated gliadin peptide IgA [Anti-DGP-IgA]) were included. Histopathology was performed on patients with the seropositive test. Marsh score > 1 considered to confirm CD. Characteristics of the Anti-tTG-IgA seropositive patients were described and that correlated with histopathologically confirmed CD were explored. Results: Of the 6,239 patients, 1.4, 2.9, 4.7, and 4.9%, were seropositive to Anti-tTG-IgG, Anti-TtG-IgA, Anti-DGP-IgA, and Anti-DGP-IgG, respectively. Overall, 7.7% were seropositive to either of the four biomarkers. Of the biopsy-screened 300 patients, 38.7% (1.9% of the total serologically screened) were confirmed with CD. The mean age of Anti-TtG-IgA seropositive patients was 32.1 ± 10.3 SD years, 72% of them were females, and 93.4% were Emirati. In those patients, overweight (28.7%) and obesity (24.7%) were common while 5.8% of patients were underweight. Anemia prevalence was 46.7%, 21.3% had Gastroesophageal reflux disease (GERD), 7.7% with autoimmune thyroid disease, 5.5% (type 1), and 3.3% (type 2) were diabetic. Vitamin D deficiency was observed in 47.8% of the Anti-TtG IgA seropositive patients. Twelve (10.3%) histopathologically confirmed CD patients were seronegative to Anti-TtG-IgA but seropositive to anti-DGP-IgA and/or Anti-DGP-IgG. Body mass index, GERD, autoimmune thyroid disease, type 1 diabetes, asthma, hemoglobin, and vitamin D concentration, were all correlated with biopsy-confirmed CD (P < 0.05). Compared to the gold-standard biopsy test, Anti-TtG-IgA had the highest sensitivity (89.7%) and specificity (83.7%). Conclusion: Three and two of every 100 patients were serologically (anti-tTG-IgA positive) and histopathologically diagnosed with CD, respectively. Although Anti-TtG-IgA is the most sensitive, specific, and commonly used test, one of every ten histopathologically confirmed patients and Anti-tTG-IgA seronegative were seropositive to Anti-DGP. To avoid missing patients with CD, a comprehensive serological investigation covering DGP-IgG/IgA is warranted.

Characterization of Pneumocystis jirovecii pneumonia at three tertiary comprehensive hospitals in southern China.

Due to the increasing use of immunosuppressant therapy, Pneumocystis jirovecii pneumonia (PJP) has become an emerging concern in human immunodeficiency virus (HIV)-negative patients. In this study, we conducted a retrospective study of 96 hospitalized patients with PJP from January 2015 to June 2019 at three tertiary comprehensive hospitals in Southern China. Information was collected regarding patient demographics, clinical manifestations, risk factors, laboratory analyses, radiological images, and treatment outcomes. PJP infection was most commonly found in middle-aged men. Kidney diseases (35.5%) and connective tissue diseases (38.7%) were the predominant risk factors for PJP. About half of the patients (48.4%) received glucocorticoid, immunosuppressant, and/or chemotherapy in a low dose or in a short-term (< 3 months). None of the patients had previously received trimethoprim-sulfamethoxazole (TMP-SMX) for PJP prophylaxis. All patients had two or more clinical manifestations (cough, dyspnea, fever, and chest pain). Biochemical investigations of CRP, ESR, PaO2, LDH, and KL-6 showed that over 90% of the patients exceeded the reference range of indicators. Our analyses revealed the dominant risk factors (HIV, kidney diseases, and connective tissue diseases) and the most consistent biochemical indicators (LDH, BG, and KL-6) for PJP. Moreover, early prophylaxis, diagnosis, and treatment should contribute to improve the survival of these PJP patients.

Diagnosis of Pneumocystis pneumonia: evaluation of four serologic biomarkers.

The diagnosis of Pneumocystis pneumonia (PCP) relies on microscopic visualization of Pneumocystis jirovecii organisms or DNA detection in pulmonary specimens. This study aimed to assess the usefulness of (1-3)-ß-d-glucan (BG), Krebs von den Lungen-6 antigen (KL-6), lactate dehydrogenase (LDH) and S-adenosyl methionine (SAM) as serologic biomarkers in the diagnosis of PCP. Serum levels of BG, KL-6, LDH and SAM were investigated in 145 Portuguese patients, 50 patients from the Netherlands, 25 Spanish patients and 40 Portuguese blood donors. Data on clinical presentation, chest imaging and gasometry tests were available. PCP cases were confirmed by microscopy and PCR techniques. A cost-effectiveness analysis was performed. BG was found to be the most reliable serologic biomarker for PCP diagnosis, followed by KL-6, LDH and SAM. The BG/KL-6 combination test was the most accurate serologic approach for PCP diagnosis, with 94.3% sensitivity and 89.6% specificity. Although less sensitive/specific than the reference standard classic methods based on bronchoalveolar lavage followed by microscopic or molecular detection of P. jirovecii organisms, the BG/KL-6 test may provide a less onerous procedure for PCP diagnosis, as it uses a minimally invasive and inexpensive specimen (blood), which may be also a major benefit for the patient's care. The BG/KL-6 combination test should be interpreted within the clinical context, and it may be used as a preliminary screening test in patients with primary suspicion of PCP, or as an alternative diagnostic procedure in patients with respiratory failure or in children, avoiding the associated risk of complications by the use of bronchoscopy.