concanavalin-a and Familial-Mediterranean-Fever

Crossed affinoimmunoelectrophoresis using concanavalin A and Aleuria aurantia lectin as diantennary glycan- and fucose-specific affinocomponents, respectively, was applied to study changes in the concentration and glycosylation of the acute phase protein alpha 1-acid glycoprotein (AGP) in sera obtained from patients with hyperimmunoglobulinemia D and periodic fever syndrome. Increases in concentration of AGP compared to control values were found not only during attacks, but also during remissions. Compared to healthy controls, the presence of diantennary glycan-containing glycoforms of AGP also increased during febrile attacks, while no changes were found during remissions. A continuous high degree of alpha 1-->3 fucosylation was accompanied by a continuous high expression of sialyl Lewisx on AGP. Despite the clinical picture of recurrent febrile attacks with asymptomatic intervals, these studies indicate that hyperimmunoglobulinemia D should be considered a condition of persistent inflammation.

Topics: Adolescent; Adult; Aged; C-Reactive Protein; Carbohydrate Sequence; Concanavalin A; Familial Mediterranean Fever; Female; Fever; Glycosylation; Humans; Hypergammaglobulinemia; Immunoglobulin D; Inflammation; Lectins; Lewis Blood Group Antigens; Male; Middle Aged; Molecular Sequence Data; Orosomucoid

The effect of colchicine on immunoregulatory T lymphocytes in children with familial Mediterranean fever (FMF) was studied. Concanavalin A (Con A)-induced suppressor cell function was significantly (P less than 0.0001) decreased in five untreated FMF patients (15 +/- 3%, mean +/- s.e.) as compared to six age matched paediatric controls (46 +/- 3%) and eight healthy adults (49 +/- 4%). When the five untreated FMF patients' mononuclear cells were pre-incubated in vitro with Con A plus 10(-5) M colchicine, their suppressor cell function was significantly increased (52 +/- 10%, P less than 0.01). Similarly, oral colchicine treatment (0.5 mg twice daily) significantly (P = 0.02) increased the five FMF patients' Con A-induced suppressor cell function to levels (34 +/- 6%) that were not significantly (P greater than 0.05) different than the paediatric controls or the healthy adults. The percentage of OKT8+ cells (but not OKT3+ or OKT4+ cells) was significantly (P less than 0.0001) decreased in 10 untreated FMF patients (16.0 +/- 0.9) as compared to 10 paediatric controls (27.6 +/- 2) or 10 healthy adults (25.7 +/- 0.6). The 10 untreated FMF patients had a significant (P less than 0.002) increase in the OKT4/OKT8 ratio (2.41 +/- 0.13) as compared to 10 FMF patients treated with 0.5 mg twice daily of colchicine (1.81 +/- 0.08), 10 pediatric controls (1.47 +/- 0.2), or 10 healthy adults (1.78 +/- 0.11). Colchicine appears to have corrected the FMF patients' elevated OKT4/OKT8 ratio by both decreasing the percentage of OKT4+ cells and increasing (but only partially correcting) the percentage of OKT8+ cells. Thus FMF patients have a suppressor cell deficiency in which colchicine treatment corrects their deficiency of Con A-induced suppressor cell function and their elevated OKT4/OKT8 ratio. This raises the possibility that colchicine might be potentially useful as an immunomodulating drug in treating patients with autoimmune or allergic diseases associated with a suppressor cell deficiency.

Topics: Adolescent; Antibodies, Monoclonal; Cell Division; Child; Child, Preschool; Colchicine; Concanavalin A; Familial Mediterranean Fever; Female; Humans; Male; T-Lymphocytes, Helper-Inducer; T-Lymphocytes, Regulatory

Topics: Adult; Cells, Cultured; Child, Preschool; Colchicine; Concanavalin A; Familial Mediterranean Fever; Humans; Immune Tolerance; Male; T-Lymphocytes, Regulatory

Defective suppressor cell function has been demonstrated in several diseases but has not been tested in familial Mediterranean fever (FMF). We tested the ability of concanavalin A-activated suppressor cells from one family with FMF to inhibit the proliferation of phytohaemagglutinin-stimulated responder cells from normal volunteers. Four FMF patients tested between acute attacks had a mean (+/- s.e.) per cent suppression (5 +/- 2) which was significantly (P less than 0.0005) less than an FMF patient tested during a spontaneous remission (47 +/- 3), 10 healthy family members (41 +/- 6) and eight normal volunteers (45 +/- 4). Since FMF is inherited as an autosomal recessive disorder, deficient suppressor cell function is expressed in homozygotes between acute attacks, but not in a homozygote in spontaneous remission, homozygotes who are phenotypically normal, nor heterozygotes. This suggests that the suppressor cell abnormality in this family is probably related to the pathogenesis of FMF rather than representing a genetic marker of FMF or non-specific depression by disease activity.

Topics: Adolescent; Adult; Aged; Child; Child, Preschool; Concanavalin A; Familial Mediterranean Fever; Female; Humans; Lymphocyte Activation; Male; Middle Aged; Pedigree; T-Lymphocytes, Regulatory; Time Factors

We have previously reported a suppressor cell deficiency in four patients with familial Mediterranean fever (FMF). Since colchicine prevents FMF attacks, we tested the effect of colchicine (1 mg twice daily) on the suppressor cell function in three of these FMF patients. Proliferation of phytohaemagglutinin-stimulated responder cells co-cultured with concanavalin A-induced suppressor cells was measured. The three FMF patients' means (+/- s.e.m.) percentage suppression of normal responder cells was markedly low before treatment (6 +/- 2) but significantly (P less than 0.001) increased during colchicine treatment (41 +/- 5) to levels similar to normal volunteers' mean percentage suppression (44 +/- 3). Colchicine corrected their suppressor cell deficiency and prevented FMF attacks during the 15 months of treatment. These findings support the hypothesis that there may be an association between these three patients' suppressor cell deficiency and the pathogenesis of their disease. Furthermore, colchicine may be potentially useful in treating patients with other diseases associated with a suppressor cell deficiency.

Topics: Adult; Aged; Child; Colchicine; Concanavalin A; Familial Mediterranean Fever; Humans; Lymphocyte Activation; Lymphopenia; Male; T-Lymphocytes, Regulatory

Topics: Adult; Aged; Child; Concanavalin A; Familial Mediterranean Fever; Humans; Immunosuppression Therapy; Male; Phytohemagglutinins