IGG Antibodies to Beta-Lactoglobulin and Cow's Milk Protein Intolerance in Down Syndrome
Pinella Failla, Concetta Barone, Rosa Pettinato and Corrado Romano
Cow's milk protein intolerance (CMPI) is the most frequent food intolerance in infancy. Its incidence ranges from 0.3 to 7.5%, according to different diagnostic criteria and clinical features. The diagnosis of CMPI is generally based on the level of IgG antibodies to beta lactoglobulin. An association of insulin-dependent diabetes mellitus (IDDM) with CMPI has been reported. CMPI in subjects with Down syndrome (DS) has been investigated by Nespoli et al. (1993) and Reichelt et al. (1994). We assayed IgG antibodies to beta-lactoglobulin, by the ELISA-method, in 78 subjects with Down syndrome and 97 mentally retarded and home-reared control subjects. Gastrointestinal disorders and IDDM was ruled out in both groups. Eleven (14.1%) and 5 (5.1%) subjects among Down syndrome group and control group respectively, were put on a CMP-free diet, and showed relief of symptoms and normalization of IgG antibodies after 6-21 months. In conclusion, CMPI appears to be more frequent in Down syndrome versus the control group and the specificity of IgG antibodies approaches 100% in our study.
Failla P, Barone C, Pettinato R, Romano C. IGG Antibodies to Beta-Lactoglobulin and Cow's Milk Protein Intolerance in Down Syndrome. Down Syndrome Research and Practice. 1998;5(3);120-122.
* From a paper presented at the 6th World Congress on Down Syndrome, Madrid,
Spain, October 1997.
Cow's milk protein intolerance (CMPI) is the most frequent food intolerance
during infancy. Its incidence ranges from 0.3 to 7.5%, depending upon diagnostic
criteria and clinical features (Walker-Smith,
Stintzing & Zetterstrom, 1979;
Host, 1994). The absence
of a reliable and specific test and the large variability of symptoms has
produced many different diagnostic criteria. The serum assay of IgG antibodies
to beta-lactoglobulin is one of the few available tests for the diagnosis
of CMPI. The association between insulin-dependent diabetes mellitus (IDDM)
and CMPI, and the increased frequency of antibodies to beta-lactoglobulin
in the serum of patients with IDDM has been reported (Dahlquist
et al., 1992;
Vaarala et al., 1996). Few papers on CMPI in people with Down syndrome
have been published. Nespoli et al. (1993) reported increased titres of
antibodies to casein and beta-lactoglobulin. Reichelt et al. (1994) found
high titres of antibodies to several food proteins, such as gliadin, casein,
alpha-lactalbumin, beta-lactoglobulin and ovalbumin. Because IgA antibodies
were increased, and only IgG antibodies to casein and gliadin were raised,
the hypothesis of an increased permeability of the intestinal mucosa towards
these antigens arose. We assayed IgG antibodies to beta-lactoglobulin in
the subjects with Down syndrome followed up in our Department in order to
assess their association with CMPI.
Subjects and Methods
IgG antibodies to beta-lactoglobulin were assayed with the ELISA method
(b-lactotest IgG, Eurospital, Trieste, Italy). The results were expressed
as an IgG index, which is the ratio between the fluorescence signal units
of the sample and the positive control multiplied by 100. An IgG index up
to 55 has been considered normal. The assay was performed on the serum of
78 subjects with Down syndrome and in 97 mentally retarded and home-reared
control subjects. None of these people had gastrointestinal disease or IDDM.
The groups were matched for age and sex. The first group (Down syndrome)
had a mean age of 11.2 years (range of 2 months-47 years) and a sex ratio
of 1.68 (M/F).
Eleven (14.1%) out of 78 subjects with Down syndrome had an increased IgG
index and nine (81.8%) of them were aged below 5 years. Only five (5.1%)
out of 97 control subjects presented an increased IgG index and four (80%)
of them were aged below 5 years. All subjects with increased IgG index showed
symptoms and/or lab exams compatible with a diagnosis of CMPI. All these
subjects were given a CMP-free diet which resulted in an improvement of
symptoms and normalization of the IgG index 6 to 21 months after the diet
was started. In the persons with Down syndrome with an increased IgG index
the main symptom was failure to thrive, and an increased frequency of anemia
was found by the laboratory tests.
As already reported (Nespoli
et al., 1993), we have found an increased incidence of IgG antibodies
to beta-lactoglobulin in the serum of people with Down syndrome compared
with a control group, and an incidence which overlaps that of the general
Stintzing & Zetterstrom, 1979;
Host, 1994). Our most
interesting result is the 100% specificity of IgG antibodies to beta-lactoglobulin
for the diagnosis of CMPI and the increased frequency below age 5 years.
IgG antibodies to beta-lactoglobulin behave differently from antigliadin
antibodies which, as reported recently (Failla
et al., 1996;
Bonamico et al., 1996), are common in people with Down syndrome, but
have low specificity for the diagnosis of coeliac disease.
Dr. Corrado Romano, Department of Pediatrics, Oasi Institute, Via Conte
Ruggero, 73, 94018 Troina (EN), Italy. (Phone 39-935-936111, Fax 39-935-653327,
Bonamico, M., Rasore-Quartino, A., Mariani, P., Scartezzini, P., Cerruti,
P., Tozzi, M.C., Cingolani, M., & Gemme, G. (1996). Down syndrome and
coeliac disease: usefulness of antigliadin and antiendomysium antibodies.
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G., Savilhati, E., & Landin-Olsson, M. (1992). An increased level of
antibodies to beta-lactoglobulin is a risk determinant for early-onset type
1 (insulin dependent) diabetes mellitus independent of islet cell antibodies
and early introduction of cow's milk. Diabetologia, 35, 980-984.
Failla, P., Ruberto, C., Pagano, M.C., Lombardo, M., Bottaro, G., Perichon,
B., Krishnamoorthy, R, Romano, C., & Ragusa, A. (1996). Celiac disease
in Down's syndrome with HLA serological and molecular studies. Journal
of Pediatric Gastroenterology and Nutrition, 23, 303-306.
- Host, A. (1994). Cow's milk protein allergy
and intolerance in infancy. Some clinical, epidemiological and immunological
aspects. Pediatric Allergy and Immunology, 5, 1-36.
Nespoli, L., Burgio, G.R., Ugazio, A.G., & Maccario, R. (1993). Immunological
features of Down's syndrome: a review. Journal of Intellectual Disability
Research, 37, 543-551.
K.L., Lindback, T., & Scott, H. (1994). Increased levels of antibodies
to food proteins in Down syndrome. Acta Paediatrica Japonica, 36,
- Stintzing, G.,
& Zetterstrom, R. (1979). Cow's milk allergy, incidence and pathogenetic
role of early exposure to cow's milk formula. Acta Paediatrica Scandinavica,
Vaarala, O., Klennetti, P., Savilahti, E., Reijonen, H., Ilonen, J., & Akerblom,
H.K. (1996). Cellular immune response to cow's milk beta-lactoglobulin
in patients with newly diagnosed IDDM. Diabetes, 45, 178-182.
- Walker-Smith, J.A. (1975). Cow's
milk protein intolerance. Archives of Disease in Childhood, 50,
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