Cellular and Humoral Immunity in Cartilage-Hair Hypoplasia

Abstract

SummaryCartilage-hair hypoplasia (CHH), a rare autosomal recessive syndrome of short-limbed growth failure, is unexpectedly common in the Finnish. An unselected series of 28 1-to 23-year-old subjects with CHH were studied for their immunologic capacity. All had been immunized with BCG as newborn, and most with vaccinia, without complications. Eight of the subjects had a history of unusually frequent infections, although none had had exceptionally severe ones. The tuberculin skin reactivity was markedly depressed: 2 of 23 subjects tested with 10 TU reacted, against twothirds of the general population of the same age. Average counts of circulating lymphocytes were subnormal in 14 of the 28 subjects, this was more frequent among the younger subjects. The counts of circulating neutrophil granulocytes were mostly normal. The serum levels of IgG, IgA, and IgM were normal, and on the average, above the mean levels for age. Sixteen of the 28 had antibodies against cow's milk, which is a very significantly increased prevalence. The numbers of immunoglobulin-containing cells in the jejunal mucosa and the concentrations of IgA and IgM in the intestinal juice were normal. The phytohemagglutinin (PHA)-induced lymphocyte transformation was below the 95% confidence range for the age in 25 of the 28 subiects, and concanavalin A (COG A)-inducei transformation was s>milarly depressed. A significant ~ositive correlation was Dresent between the counts of circulating lymphocytes and the PHA-induced lymphocyte transformation: the lymphopenia is presumably predominantly due to a decrease in the number of PHA-responding lymphocytes. The PPD-induced lymphocyte transformation was also depressed; this was in significant correlation with the depression of skin reactivity to tuberculin. The proportion of T cells of circulating lymphocytes, as judged with the E rosette test, was decreased but still unexpectedly high in view of the degree of depression of PHA response. Varicella was observed in the subject who previously had the lowest PHA response. Her disease was clinically mild and her response with an increase in the circulating lymphoblasts was normal. Impairment of cellular immunity, although variable in degree, is evidently an integral part of the CHH syndrome, and at least as constant as the hair abnormality. Speculation in which a deficiency of the immune system is associated with growth failure and/or abnormalities of hair and skin (5,6,27). Lux et al. (19) made an immunologic study of two children with CHH, selected because of a history of severe varicella. Persistent lymphopenia, diminished delayed skin test sensitivity, and decreased in vitro responsiveness of lymphocytes to PHA were observed.The prevalence of CHH is exceptionally high in the Finnish population (21, 22). We have carried out a clinical and immunologic study of 28 consecutive cases of CHH referred to our clinic for growth disorders. Some of them had suffered from recurrent respiratory tract infections, but none from very severe viral infections. The immunologic fi...

Impaired culture generated cytotoxicity with preservation of spontaneous natural killer-cell activity in cartilage-hair hypoplasia.

“…Both CHH CTCL showed diminished cytotoxicity against K562 targets when tested after 20 d of culture (Table V) (Table V). DISCUSSION Marked impairment of lymphocyte proliferation has been described in cartilage-hair hypoplasia (2)(3)(4)(5). In and all were E+ and Fcy-.…”

“…Cartilage-hair hypoplasia (CHH)' is an autosomal recessive form of short-limbed dwarfism, which is found in increased frequency in the Old Order Amish of the United States, as well as in the Finnish population (1,2). It is characterized by short stature, sparse unpigmented hair, and cellular immunodeficiency (1)(2)(3)(4).…”

“…It is characterized by short stature, sparse unpigmented hair, and cellular immunodeficiency (1)(2)(3)(4). CHH individuals have decreased numbers of circulating B and T lymphocytes, negative delayed-type hypersensitivity reactions, and severely depressed proliferative responses to B and T cell specific antigens and mitogens.…”

“…Only a minority of CHH individuals suffer severe, sometimes fatal, viral infections (1)(2)(3). Thus, we sought to identify immunological mechanisms present in CHH that might account for this apparent paradox.…”

Cartilage-hair hypoplasia — clinical manifestations in 108 Finnish patients

“…Impairment of cellular immunity is indicated by lymphopenia and decreased in vitro lymphocyte reactivity; humoral immunity is intact [28,39]. Deficient erythrocyte production often presents as mild transient macrocytic…”