RESUMEN
A 5-year-old female diagnosed with severe hemophilia B began experiencing frequent muscular and joint bleeds at 19 months old. Molecular studies, including Sanger sequencing, Giemsa banding, human androgen receptor (HUMARA) assay, array-based comparative genomic hybridization (aCGH), whole-exome sequencing (WES), and multiplex ligation-dependent probe amplification (MLPA), revealed a heterozygous factor IX (F9) intron 3 substitution (c.277+1G>T) inherited from her mother and a de novo heterozygous 441 kb deletion in the Xq28 region, which flanked intron 22 homologous regions 1 (int22h1) and 2 (int22h2). This rare genetic profile explains her severe phenotype and guides hereditary consultation for family planning.
RESUMEN
OBJECTIVE: Haemophilia A and B are disorders caused by the lack of clotting factors VIII and IX, respectively. Repeated bleeding into the same joint leads to haemophilic arthropathy (HA). Interleukin (IL)-1ß is responsible for the pro-inflammatory response and IL-37 is induced by IL-1ß stimuli to have an anti-inflammatory response and prevent uncontrolled inflammation and tissue damage. Our objective was to investigate plasma levels of IL-1ß and IL-37 in patients with severe haemophilia with different severities of HA. METHODS: Peripheral blood samples were collected from 14 patients with severe haemophilia A and 6 with severe haemophilia B, and 18 healthy individuals. Plasma levels of IL-1ß and IL-37 were detected by immunoassay, and severity of HA was evaluated using the Pettersson scoring system. Plasma levels of IL-1ß and IL-37 were analysed in patients with severe haemophilia grouped by Pettersson score and in healthy individuals. RESULTS: Plasma levels of IL-1ß and IL-37 were significantly higher in patients with severe haemophilia compared with healthy individuals and significantly lower in those with moderate to severe HA than in those with no or mild HA. CONCLUSIONS: Plasma levels of IL-1ß and IL-37 may be useful to track HA progression in patients with severe haemophilia.