Frequency and causes of respiratory tract infections and its association with mannose-binding lectin in patients with familial mediterranean fever

Familial Mediterranean fever (FMF) is a systemic, auto-inflammatory isorder with autosomal inheritance which is characterized by irregular relapses and self-limited fever, peritonitis, synovitis, pleuritis and/or skin eruptions. To best of our knowledge, there is no study on frequency of upper respiratory tract infections in patients with FMF in the literature. This frequency of respiratory tract infections and its association to mannose-binding lectin was investigated for the first time in this study. The study included 50 patients aged 3-18 years who were diagnosed as MF and followed in Pediatric Nephrology Department of Akdeniz University, 82 Medicine School and age- and sex-matched 20 healthy children, who presented to pediatrics outpatient clinic with reasons other than infection (e.g. obesity, constipation, hypothyroidism) and had no family history of FMF or symptoms suggesting FMF and no finding of chronic inflammation in physical examination and laboratory evaluations, were employed as control group. The study was conducted between June, 2014 and May, 2014. A data sheet was developed for the patient and control groups. Age, gender, annual incidence of upper respiratory tract infection, annual incidence of pneumonia, otitis media, bronchiolitis and urinary tract infection, history of acute rheumatoid fever, allergy and gastroesophageal reflux and results of immune deficiency screening developed by Jeffrey Model Foundation were recorded. Complete blood count and levels of ASO, pediatric IgA, IgM, IgE and IgG, CRP, SAA, MBL, anti-Hbs antibody, C3 and C4 were studied in both patient and control groups. Urinalysis was performed including urinary protein and creatinine measurements. There were 33 boys (66%) and 17 girls (34%) in the patient group while 7 boys (%35) and 13 girls (65%) in the control group. Mean age was 11.0±4.6 years in the patient group while 11.9±4.2 years in the control group. In this study, "frequent upper tract infection" was defined as 8 or more upper respiratory tract infection per year. It was found that 10 of patients with FMF had frequent upper respiratory tract infection while no patient in the control group had frequent upper respiratory tract infection. A significant difference was found between the patient and control groups. The cases with age-adjusted serum IgA, IgM, C3 and C4 values <-2 SDS in the FMF and control groups were compared and no significant difference was found between groups. However, a significant differences was detected when the cases with age-adjusted serum IgG values<-2 SDS in the FMF and control groups were compared The FMF patients with age-adjusted serum IgA, IgG, IgM, C3, C4 and MBL values<-2SDS and frequent upper respiratory infection were compared to those with age-adjusted serum IgA, IgG, IgM, C3, C4 and MBL values<-2SDS and infrequent upper respiratory tract infection. No significant difference was 83 found between groups. The correlation between frequency of upper respiratory tract infection and serum IgA, IgG, IgM, IgE, C3, C4, MBL and ASO levels were assessed. No significant correlation was detected between serum IgM, C3, C4, MBL levels and frequency of upper respiratory tract. When median serum MBL levels were compared between FMF patients and controls, no significant difference was found between groups. In our study, cut-off value for MBL deficiency was defined as <600 ng/ml. The FMF patients and controls were stratified according to this MBL cut-off value: those with MBL<600 ng/ml and those with MBL≥600 ng/ml. Serum MBL level was found to be low in 10 FMF patients (20%) and in 2 controls (%10). No significant difference was detected when two groups were compared (0=.336). A weak negative correlation was detected between frequency of upper respiratory tract infection and serum IgA level which didn't reach statistical significance. A weak- to-moderate negative correlation was detected between frequency of upper respiratory tract infection and serum IgE level which didn't reach statistical significance. Our results showed that FMF patients had upper respiratory tract infection more frequently than controls. AAA of patients with IgG levels were significantly lower than the control group However The FMF patients with low serum IgA, IgG, IgM, C3, C4 and MBL and frequent upper respiratory infection were compared to those with low serum IgA, IgG, IgM, C3, C4 and MBL and infrequent upper respiratory tract infection. No significant difference was found between groups. Further comprehensive studies are needed as number of patients is much higher. Keywords: Familial Mediterranean fever, frequent upper respiratory tract infection, mannose-binding lectin