ABSTRACT
BACKGROUND: Autoimmune neutropenia of infancy (AIN) is a frequent cause of neutropenia in children. The disease is caused by antibodies against epitopes on the immunoglobulin G (IgG) Fc receptor type 3b (FcγIIIb). We investigated the possible association of human neutrophil antigens (HNA), human leukocyte antigen (HLA)-DR, and HLA-DQ alleles with AIN and the association of these genotypes with the presence of autoantibodies. METHODS: Eighty AIN cases with a median age of 13.5 months were included. Controls were healthy unrelated Danish blood donors. Anti-HNA-1a autoantibodies were detected using a flow cytometric granulocyte immunofluorescence test (Flow-GIFT) with phenotyped donor cells for detection of antibody specificity. Molecular determination of HNA genotypes was determined using real-time polymerase chain reaction (q-PCR). High-resolution HLA-DRB1 and HLA-DQB1 were determined by next-generation sequencing. RESULTS: Antibodies against HNA-1a were detected in 51% (n = 41) of AIN patients, and anti-HNA-1b was detected in 3% (n = 2) of cases. In 46% of cases, the antibodies were anti-FcγIIIb-reactive. FCGR3B*01+,*02-,*03- was more common (odds ratio, 6.70; P < .0001), and FCGR3B*01-,*02+,*03- was less common (odds ratio, 0.30; P < .0001) among AIN cases. HNA-1a antibodies were significantly more frequent among AIN cases with the FCGR3B*01+,*02-,*03- genotype (odds ratio, 3.86; P < .007). The HLA-DRB1*14 - HLA-DQB1*05:03 haplotype was significantly more common (odds ratio, 7.44; P < .0001) in AIN patients. CONCLUSION: The HLA haplotype HLA-DRB1*14 - DQB1*05:03 is associated with Danish AIN cases. Among Danish AIN patients, anti-HNA-1a is the most common autoantibody, and the antibody is more common in cases with the FCGR3B*01+,*02-,*03- genotype.
Subject(s)
Neutropenia , Neutrophils , Autoimmunity , Denmark , Genotype , HLA Antigens , Humans , InfantABSTRACT
BACKGROUND: Testing stimulates learning, improves long-term retention, and promotes technical performance. No purpose-orientated test of competence in the theoretical aspects of VATS lobectomy has previously been presented. The purpose of this study was, therefore, to develop and gather validity evidence for a theoretical test on VATS lobectomy consisting of multiple-choice questions. METHODS: Four European VATS lobectomy experts were interviewed to explore their views on important theoretical VATS lobectomy knowledge (step 1). This information was used to construct the test items in compliance with existing guidelines for multiple-choice questions (step 2). The experts rated the relevance of the items to confirm content validity in a modified Delphi approach (step 3). Finally, the test was administered to physicians, who were categorised into different experience levels based on their experience in VATS procedures overall and in VATS lobectomies specifically. Their answers were used to achieve construct validity (step 4). RESULTS: Initially, 81 items were constructed and two Delphi iterations reduced the test to 50 items. Item analysis led to the exclusion of 19 items and the mean discrimination index of the 31 final items was 0.26. Cronbach's alpha for internal consistency was 0.75. The mean item difficulty was calculated to 0.63. According to performed VATS procedures, significantly different test performances were detected when comparing the group performances (p = 0.002) and the experts performed significantly better than the novices (p < 0.001) and intermediates (p = 0.01). In the category of performed VATS lobectomies, significant group performances were also found. In this category, the experts were also significantly better than the novices (p < 0.001), the trainees (p = 0.002), and the intermediates (p = 0.01). CONCLUSIONS: This study led to the development of a theoretical test on VATS lobectomy consisting of multiple-choice questions. Both content and construct validity evidence were established.
