A milk-free diet downregulates folate receptor autoimmunity in cerebral folate deficiency syndrome

Adult; Animals; Autoantibodies; Autoimmunity; Brain; Carrier Proteins; Child; Child, Preschool; Diet, Reducing; Down-Regulation; Enzyme-Linked Immunosorbent Assay; Female; Folic Acid Deficiency; Humans; Infant; Male; Milk; Receptors, Cell Surface; Statistics, Nonparametric; Time Factors

Abstract :

[en] In cerebral folate deficiency syndrome, the presence of autoantibodies against the folate receptor (FR) explains decreased folate transport to the central nervous system and the clinical response to folinic acid. Autoantibody crossreactivity with milk FR from different species prompted us to test the effect of a milk-free diet. Intervention with a milkfree diet in 12 children (nine males, three females; mean age 6y [SD 4y 11mo], range 1-19y), decreased autoantibody titer significantly from 2.08pmol of FR blocked per ml of serum (SD 2.1; range 0.24-8.35) to 0.35pmol (SD 0.49; range 0-1.32; p=0.012) over 3 to 13 months, whereas FR autoantibody titer increased significantly to 6.53 (SD 6.08; range 0.54-14.07; p=0.013) in nine children who were reexposed to milk for 6 to 14 weeks. In 12 children on a normal diet (eight males, four females; mean age 5y 5mo [SD 4y 1mo], range 1y 6mo-16y 4mo), the antibody titer increased significantly from 0.84pmol of FR blocked per ml (SD 0.39; range 0.24-1.44) to 3.04pmol (SD 1.42; range 0.84-6.01; p=0.001) over 10 to 24 months. Decreasing the autoantibody titer with a milk-free diet in conjunction with folinic acid therapy may be advocated for these patients. © 2008 Blackwell Publishing Ltd.

Disciplines :

Pediatrics
Endocrinology, metabolism & nutrition
Neurology

Author, co-author :

Ramaekers, Vincent ; Université de Liège - ULiège > Relations académiques et scientifiques (Médecine)

Sequeira, J. M.; Departments of Medicine and Cell Biology, SUNY - Downstate Medical Center, Brooklyn, NY, United States

Blau, N.; Division of Chemistry and Biochemistry, University Children's Hospital, Zurich, Switzerland

Quadros, E. V.; Departments of Medicine and Cell Biology, SUNY - Downstate Medical Center, Brooklyn, NY, United States, SUNY -Downstate Medical Center, 450 Clarkson Avenue, Brooklyn, NY 11203, United States

Language :

English

Title :

A milk-free diet downregulates folate receptor autoimmunity in cerebral folate deficiency syndrome

Publication date :

May 2008

Journal title :

Developmental Medicine and Child Neurology

ISSN :

0012-1622

eISSN :

1469-8749

Publisher :

Wiley-Blackwell, United States

Volume :

Issue :

Pages :

346-352

Peer reviewed :

Peer Reviewed verified by ORBi

Commentary :

Epub 2008 Mar 19

Available on ORBi :

since 30 May 2014

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Bibliography

Ramaekers VT, Hausler M, Opladen T, Heimann G, Blau N. Psychomotor retardation, spastic paraplegia, cerebellar ataxia and dyskinesia associated with low 5-methyltetrahydrofolate in cerebrospinal fluid: A novel neurometabolic condition responding to folinic acid substitution. Neuropediatrics 2002; 33: 301-08.
Ramaekers VT, Blau N. Cerebral folate deficiency. Dev Med Child Neurol 2004; 46: 843-51.
Holm J, Hansen SI, Hoier-Madsen M, Bostad L. High-affinity folate binding in human choroid plexus. Characterization of radioligand binding, immunoreactivity, molecular heterogeneity and hydrophobic domain of the binding protein. Biochem J 1991; 280: 267-71.
Spector R, Johanson C. Micronutrient and urate transport in choroid plexus and kidney: Implications for drug therapy. Pharm Res 2006; 23: 2515-24.
Rothenberg SP, da Costa MP, Sequeira JM, et al. Autoantibodies against folate receptors in women with a pregnancy complicated by a neural-tube defect. N Engl J Med 2004; 350: 134-42.
Ramaekers VT, Rothenberg SP, Sequeira JM, et al. Autoantibodies to folate receptors in the cerebral folate deficiency syndrome. N Engl J Med 2005; 352: 1985-91.
Schwartz RS. Autoimmune folate deficiency and the rise and fall of 'horror autotoxicus'. N Engl J Med 2005; 352: 1948-50.
Jefferis R, Reimer CB, Skvaril F, et al. Evaluation of monoclonal antibodies having specificity for human IgG sub-classes: Results of an IUIS/WHO collaborative study. Immunol Lett 1985; 10: 223-52.
Hamilton RG, Reimer CB, Rodkey LS. Quality control of murine monoclonal antibodies using isoelectric focusing affinity immunoblot analysis. Hybridoma 1987; 6: 205-17.
Reimer CB, Phillips DJ, Aloisio CH, et al. Evaluation of thirty-one mouse monoclonal antibodies to human IgG epitopes. Hybridoma 1984; 3: 263-75.
Forssen KM, Jagerstad MI, Wigertz K, Witthoft CM. Folates and dairy products: A critical update. J Am Coll Nutr 2000; 19 (Suppl. 2): 100S-110S.
Bowcock AM, Lovett M. Zeroing in on tolerance. Nat Med 2001; 7: 279-81.
Ohashi PS. T-cell signalling and autoimmunity: Molecular mechanisms of disease. Nat Rev Immunol 2002; 2: 427-38.
Pearce SH, Merriman TR. Genetic progress towards the molecular basis of autoimmunity. Trends Mol Med 2006; 12: 90-98.
Pearson WR, Lipman DJ. Improved tools for biological sequence comparison. Proc Natl Acad Sci USA 1988; 85: 2444-48.
Antony AC. The biological chemistry of folate receptors. Blood 1992; 79: 2807-20.
Henderson GB. Folate-binding proteins. Annu Rev Nutr 1990; 10: 319-35.
Aalberse RC, van der Gaag R, van Leeuwen J. Serologic aspects of IgG4 antibodies. I. Prolonged immunization results in an IgG4-restricted response. J Immunol 1983; 130: 722-26.
Ottesen EA, Skvaril F, Tripathy SP, Poindexter RW, Hussain R. Prominence of IgG4 in the IgG antibody response to human filariasis. J Immunol 1985; 134: 2707-12.
Hernandez-Diaz S, Werler MM, Walker AM, Mitchell AA. Folic acid antagonists during pregnancy and the risk of birth defects. N Engl J Med 2000; 343: 1608-14.
Finnell RH, Gelineau-van Waes J, Bennett GD, et al. Genetic basis of susceptibility to environmentally induced neural tube defects. Ann NY Acad Sci 2000; 919: 261-77.
Ramaekers VT, Sequeira JM, Artuch R, et al. Folate receptor autoantibodies and spinal fluid 5-methyltetrahydrofolate deficiency in Rett syndrome. Neuropediatrics 2007; 38: 179-83.
Ramaekers VT, Blau N, Sequeira JM, Nassogne MC, Quadros EV. Folate receptor autoimmunity and cerebral folate deficiency in low-functioning autism with neurological deficits. Neuropediatrics (Forthcoming).