RESULTS
The baseline characteristics of the 81 participants were similar in the gender distribution (Female=37 (45.7%), the median age of onset of neutropenia was 3.7 months (1.1- 48)). The majority of patients presented with infection (n=39, 48.1%), predominantly viral infection (n= 26, 66.7%), whilst invasive infection in the form of abscess made up 15.4%. No patients from this cohort developed bacteremia, invasive respiratory, central nervous system, urinary tract or bone infection at presentation. The second most common presentation was incidental finding from blood taking in neonates with prolonged neonatal jaundice (n= 27, 33.3%), the rest made up by incidental finding during investigation for other conditions including failure to thrive, premature thelarche, congenital cataract and per rectal bleeding. Among these 27 infants picked up by neonatal jaundice screening, only 3/27 had detectable anti-neutrophil antibodies, 2/27 had persistent neutropenia during the period of follow up whilst the rest recovered, their median time to recover was 1.61 years which was shorter than the 2.65 years of the whole cohort. In the 81 participants with presumed CBN, anti-neutrophil antibodies were detected in 30.9% (n=25) of individuals. Antibodies against HNA-1a was detected in 21 individuals, whilst 4 were against HNA-3a. When comparing those with anti-neutrophil antibodies versus without (Table 1), AIN patients were significantly older in age of onset (median, 6.7 versus 2.1 months, p=0.0029), more likely to have severe neutropenia on presentation (neutrophil count <0.5 x 109/L, p=0.0437), more individuals with profound neutropenia (neutrophil count <1 x 109/L, p=0.0152) with the lowest neutrophil count also found to be lower (0.1 x 109/L versus 0.4 x 109/L, p=0.0005) and more likely to have invasive infection (n= 6, 24% versus n=4, 7.1%, p=0.041). The majority of invasive infection occurred in the first year of diagnosis. Abscess was the most common presentation and involvement varied from skin, submandibular, perianal and in the finger. Methicillin-sensitive Staphylococcal aureus was the most commonly cultured bacteria.
The time for 50% recovery probability for this cohort of neutropenia patients was 2.34 years from onset (95% C.I. 1.98 to 2.71). (Fig. 1A) Furthermore, anti-neutrophil antibody positive individuals were found to recover slower and later, based on the reverse Kaplan-Meier curve, it can be deduced that at 5 years follow up, 87.9% of anti-neutrophil antibody negative individuals recovered versus 69% of antineutrophil antibody positive individuals (p=0.035). (Fig. 1B) Cox regression analysis found that the anti-neutrophil antibody status was independently associated with neutropenia recovery, where those with antibody-negative status had a 1.87 times higher chance of neutropenia recovery compared to antibody-positive individuals irrespective of follow-up time and age of onset.
Amongst the 81 samples processed, other than for 11 samples, the rest of the results were concordant amongst the three tests used. Among the discrepant samples, LABScreen MULTI detected anti-neutrophil antibodies in 9 samples, which was not detected by GIFT and GAT. Whilst for 2 samples, LABScreen MULTI was negative and GIFT or GAT detected anti-neutrophil antibodies against HNA-3a antigen.