Selected Abstracts from the 13th Annual Meeting of the Clinical Immunology Society: 2022 Annual Meeting: Immune Deficiency and Dysregulation North American Conference

Journal of Clinical Immunology - Coronavirus disease 2019 (COVID-19) exhibits a wide spectrum of clinical manifestations, ranging from asymptomatic to critical conditions. Understanding the...     

Itolizumab,a novel anti-CD6 monoclonal antibody: a safe and efficacious biologic agent for management of psoriasis

Introduction: Psoriasis, a chronic immune-mediated skin disorder is associated with significant physical, psychological, and quality of life impairments. Along with well-documented genetic and environmental factors, immunological factors also contribute to the pathogenesis of psoriasis. Among the immunological factors, CD6 – dependent T-cell proliferation to form Th1 and Th17 cells play a major role in the pathogenesis of psoriasis. Itolizumab is the first humanized IgG1 monoclonal antibody, which selectively targets CD6.

Areas covered: The current article presents the pharmacology of itolizumab and provides a review of the currently available data on the efficacy and safety of itolizumab for management of moderate to severe plaque psoriasis.

Expert opinion: The use of biologics to attenuate the immune-mediated pathological events in psoriasis is a relatively well-established clinical practice. However, the safety and efficacy of biologics continues to be an unsettled topic of ongoing research. While available data seems to suggest that itolizumab may be a safer option, additional studies with higher sample sizes and active comparators are needed before definitive conclusions can be drawn on the place of itolizumab in the management of psoriasis.     

Macrocheilia due to lymphangiectasia.

A case of symmetrical, diffuse macrocheilia due to lymphangiectasia is presented. No primary cause for this case or for many other pathologic forms of macrocheilia has been established. Tranverse mucosal wedge resection of the lip with mucosal advancement, however, is a satisfactory method of treatment.     

Histologic Risk Factors and Clinical Outcome in Colorectal Malignant Polyp: A Pooled-Data Analysis

PURPOSE The malignant polyp carries a significant risk of lymphohematic metastasis and mortality. Clinical usefulness of histologic risk factors is still controversial. The study was designed to compute the association between the main histologic risk factors and the occurrence of unfavorable outcomes in patients with malignant polyps.METHODS A MEDLINE search regarding malignant polyps was performed. Three histologic risk factors (positive resection margin, poor differentiation of carcinoma, vascular invasion) and five (residual disease, recurrent disease, lymph node metastasis, hematogenous metastasis, mortality) unfavorable clinical outcomes were evaluated. Further analysis was performed by subgrouping polyps in high-risk and low-risk groups.RESULTS Thirty-one studies enrolling 1,900 patients with malignant polyp were selected. Positivity of resection margin was significantly predictive of the presence of residual disease (odds ratio, 22; P < 0.0001), poorly differentiated carcinoma was associated with an increased mortality (odds ratio, 9.2; P < 0.05), and vascular invasion with a higher lymph node metastasis risk (odds ratio, 7; P < 0.05). Patients with high-risk polyps showed a significantly worse outcome than those with low-risk, especially for mortality (odds ratio, 11; P < 0.05). Surgical-related death was as low as 0.8 percent.CONCLUSIONS All three histologic risk factors are significantly associated with the clinical outcome. Classification in low-risk and high-risk patients may be regarded as a meaningful staging procedure.     

Unusual presentation of gallstones

Gallstones are usually asymptomatic in the majority of patients. Gallstones can migrate through a cholecysto-duodenal fistula and may cause an intestinal obstruction anywhere along the gastrointestinal tract. The obstruction usually occurs at the level of the ileocecal valve. In most cases, the clinical presentation includes symptoms related to the intestinal obstruction including abdominal pain and vomiting. We report an unusual case of gallstones presented with acute prerenal azotemia as the major manifestation.     

Augmentation of lipopolysaccharide-induced nitric oxide production by alpha-galactosylceramide in mouse peritoneal cells

The effect of alpha-galactosylceramide (alpha-GalCer) on lipopolysaccharide (LPS)-induced nitric oxide (NO) production in mouse peritoneal cells was studied. alpha-GalCer augmented LPS-induced NO production in mouse peritoneal cells, but not in RAW 264.7 macrophage cells. alpha-GalCer augmented NO production, but not tumor necrosis factor (TNF)-alpha production in LPS-stimulated peritoneal cells. Peritoneal cells produced a significant level of interferon (IFN)-gamma in response to alpha-GalCer and anti-IFN-gamma antibody abolished the augmentation of LPS-induced NO production by alpha-GalCer. Moreover, anti-IFN-gamma antibody prevented the enhanced expression of an inducible type of NO synthase mRNA by alpha-GalCer. alpha-GalCer did not augment LPS-induced NO production in peritoneal cells from natural killer T (NKT)-deficient mice. Therefore, it was suggested that alpha-GalCer might augment LPS-induced NO production in peritoneal cells through release of IFN-gamma from NKT cells.     

Imipenem Treatment Induces Expression of Important Genes and Phenotypes in a Resistant Acinetobacter baumannii Isolate

Acinetobacter baumannii has emerged as a notorious multidrug-resistant pathogen, and development of novel control measures is of the utmost importance. Understanding the factors that play a role in drug resistance may contribute to the identification of novel therapeutic targets. Pili are essential for A. baumannii adherence to and biofilm formation on abiotic surfaces as well as virulence. In the present study, we found that biofilm formation was significantly induced in an imipenem-resistant (Imp^r) strain treated with a subinhibitory concentration of antibiotic compared to that in an untreated control and an imipenem-susceptible (Imp^s) isolate. Using microarray and quantitative PCR analyses, we observed that several genes responsible for the synthesis of type IV pili were significantly upregulated in the Imp^r but not in the Imp^s isolate. Notably, this finding is corroborated by an increase in the motility of the Imp^r strain. Our results suggest that the ability to overproduce colonization factors in response to imipenem treatment confers biological advantage to A. baumannii and may contribute to clinical success.     

Serum vitamin D levels correlate to coronary artery disease severity: a retrospective chart analysis

Background: The pro-atherosclerotic nature of vitamin D deficiency has been shown to increase cardiovascular events. We further emphasized and evaluated the severity of coronary artery disease (CAD) with varying levels of vitamin D in relation to age, gender, ethnicity and baseline confounders.

Methods: A retrospective, single-center study of 9,399 patients admitted between 2005 and 2014 for chest pain who underwent coronary angiography. Patients without a vitamin D level, measured as 25-dihydroxyvitamin D (25[OH]D) were excluded from our study. 25(OH)D deficiency and insufficiency were defined by having serum concentration levels of less than 20 ng/ml and 20 to 29.9 ng/ml, respectively, while normal levels were defined as greater than or equal to 30 ng/ml. We assessed levels of 25(OH)D and extent of coronary disease with coronary angiography as obstructive CAD (left main stenosis of ≥50% or any stenosis of ≥70%), non-obstructive CAD (≥1 stenosis ≥20% but no stenosis ≥70%) and normal coronaries (no stenosis >20%).

Results: Among 9,399 patients, 1,311 qualified, of which 308 patients (23%) had normal 25(OH)D levels, 552 patients (42%) had 25(OH)D deficiency and 451 patients (35%) had 25(OH)D insufficiency. In an analysis of the extent of coronary disease, we identified 20% of patients having normal coronaries, 55% having obstructive CAD and 25% having non-obstructive CAD. Baseline clinical risk factors and co-morbidities did not differ between the groups.

Patients with normal 25(OH)D levels were found to have normal coronaries compared to patients with 25(OH)D deficiency or insufficiency (OR: 7, 95% CI: 5.2 – 9.5, p < 0.0001). Comparing patients with normal 25(OH)D levels, patients with 25(OH)D deficiency or insufficiency (<29 ng/ml), 62% were found to have obstructive CAD (n = 624, OR: 2.9, 95% CI: 2.3-3.7, p < 0.0001) and 25% had non-obstructive CAD (n = 249, OR: 1.5, 95% CI: 1.1-2, p = 0.02).

Conclusion: Normal coronaries and CAD were shown to correlate with normal and low levels of 25(OH)D, respectively. There is an inverse relationship between the percentage of coronary artery occlusion and serum 25(OH)D concentrations. Vitamin D may provide benefits in risk stratification of patients with CAD and serve as a possible risk factor.