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.