HUMORAL IMMUNITY IN CHILDREN WITH CYSTIC FIBROSIS(CF) AND CHRONIC LIVER DISEASE (CLD)

Abstract

Altered immune status as evidenced by inappropriate immune reactions to liver membrane antigens occurs in children with CF and CLD, who also have an increased frequency of the “autoimmune” haplolype HLA B8-DR3. To determine whether immune alterations typical of other autoimmune liver disease were present we investigated 143 children with CF, including 25 with CLD. Immunoglobulin levels were measured by nephelometry and autoantibodies (AA) to nuclear (ANA), nucleolar (ANoA), mitochrondrial (AMA), smooth muscle (SMA), gastric parietal cell (GPC) and liver, kidney microsomal (LKM) antigens by indirect immunofluorescence using rat kidney, liver and gut and HEp-2 cells as substrate.IgG and IgA were significantly higher in children with LD than in those without (p<0.005 and <0.007 respectively) whereas IgM levels were similar. AA were found in 96 (67%) children (titres 1:10 to 1:40, median 1:10) : ANA in 56 (39%); ANoA in 55 (38%); SMA in 21 (15%); GPC in 13 (9%); AMA in 2 (1.3%); LKM in 1 (1%). The frequency of AA was similar in children with and without LD but occurred in <2% of normal age matched controls.Humoral immune abnormalities typical of auto immune diseases are frequent in CF. Their pathophysiological role in CF is unclear. AA including a high and previously unreported incidence of ANoA may arise from recurrent stimulation of the immune system by infection and/or tissue disruption but are not related to LD. High IgG and IgA in CF with CLD may derive from defective clearance by the liver.