Low thymic output and reduced heterogeneity of alpha/beta, but not gamma/delta, T lymphocytes in infants with ataxia-telangiectasia.

Ataxia-telangiectasia, a genetic disease caused by the homozygous mutation of the ATM gene, is frequently associated to a deficit of humoral and cellular immune functions. A decreased thymic output and skewed T cell and B cell receptor repertoires have been recently described in children over 7 years of age and in adults with this disease and have been proposed as a possible explanation for the immunodeficiency. To understand whether T cell defects arise early in life as a consequence of ATM gene mutations, we analysed the extent of thymic function by measuring the number of naïve T cells and by studying the heterogeneity of T cells by means of heteroduplex analysis, in two children less than 2 years old with a remarkable reduction of T cell count. We found that the thymic output is decreased in babies with ataxia-telangiectasia if compared with that observed in age-matched normal babies. The low production of new T cells is associated to a reduction of the diversity of alpha/beta, but not gamma/delta, T lymphocytes. Our data indicate that ATM mutation limits the generation of a wide alpha/beta T cell repertoire and this feature can be responsible for the immunodeficiency observed in ataxia-telangiectasia babies.

Impaired thymic output and restricted T-cell repertoire in two infants with immunodeficiency and early-onset generalized dermatitis.

We evaluated the T-cell repertoire and the thymic output in two infants, one with Omenn Syndrome (OS) and another with complete DiGeorge Syndrome (DGS), who developed generalized dermatitis. The patients shared common T-cell abnormalities, as demonstrated by the low response to mitogenic stimulation, by an unusual usage of specific T-cell receptor (TCR) segments, and by a reduction of TCR diversity in both alpha/beta and gamma/delta populations. Furthermore, they both showed an impaired thymic function, as assessed by the low number of TCR recombination excision circles, which are formed from excised DNA during the rearrangement of TCR genes. These data indicated that generalized erythrodermia may be present in different forms of T-cell immunodeficiency and may reflect intrinsic defects in either V(D)J recombination or in thymic development, leading to the peripheral expansion of T-cell clonotypes, that bear peculiar TCR chains.

Restriction of T-cell receptor repertoires in idiopathic CD4+ lymphocytopenia.

We report that alpha/beta and gamma/delta T-cell repertoires of three patients with idiopathic CD4+ lymphocytopenia, who showed different clinical manifestations and outcomes over time, were highly restricted. The disruption of T-cell repertoires does not influence the susceptibility to infections: the first patient was unable to attain a protective response to mycobacterium, the second showed clinical improvement and the third did not develop opportunistic infections. These results indicate that idiopathic CD4+ lymphocytopenia could give rise to mono-/oligoclonal T-cell expansions, but the degree of repertoire disturbance is not indicative of the severity of disease progression.

Development of autologous T lymphocytes in two males with X-linked severe combined immune deficiency: molecular and cellular characterization.

We report on two patients affected with severe combined immune deficiency (SCID) with an unusual immunological phenotype and a substantial number of autologous, poorly functioning T cells. Distinct mutations identified at the IL2RG locus in the two patients impaired IL-2-mediated signaling but affected T-cell lymphopoiesis differently, resulting in generation of a polyclonal or oligoclonal T-cell repertoire. These observations add to the growing complexity of the immunological spectrum of SCID in humans and indicate the need for detailed immunological and molecular investigations in atypical cases.

Intrathymic restriction and peripheral expansion of the T-cell repertoire in Omenn syndrome.

Mutations in the human RAG genes that impair, but do not abolish, recombination activity lead to Omenn syndrome, a severe primary immune deficiency that is associated with clinical and pathological features of graft-versus-host disease and oligoclonal expansion of activated, autologous T cells. We have analyzed the mechanisms accounting for peripheral oligoclonality of the T-cell repertoire. Predominance of few T-cell receptor clonotypes (both within TCRAB- and within TCRGD-expressing lymphocytes) is already detectable in the thymus and is further selected for in the periphery, with a different distribution of clonotypes in different tissues. These data indicate that oligoclonality of the T-cell repertoire in Omenn syndrome is due both to intrathymic restriction and to peripheral expansion. Moreover, the RAG genes defect that causes Omenn syndrome directly affects early stages of V(D)J recombination, but does not alter the process of double-strand-break DNA repair, including N and P nucleotide insertion.

[Abdominal migraine simulating acute abdomen]. / Emicrania addominale simulante addome acuto.

Migraine is a variant of headache often associated with neurologic and/or vegetative symptoms mainly represented by abdominal pain. This symptom may occur some hours before migraine manifestation and in these cases the differential diagnosis with other clinical conditions characterized by abdominal pain, which is very common during childhood, may be difficult. Abdominal migraine can be diagnosed only if a close relationship is demonstrated between the abdominal symptoms and migraine. Alteration of consciousness is a well known feature during migraine and in some cases EEG may show SNC involvement during the attack. We report a case of abdominal migraine attack evaluated by EEG. The patient, a 10 years old male, presented with a picture of acute abdomen. An EEG performed at the occurrence of the early headache symptoms and of consciousness alteration demonstrated a pattern characterized by a lowering in the electric activity on the left hemisphere. Some hours later he developed a clear migraine followed by disappearance of the abdominal symptoms. This observation confirms the possible association of migraine with a picture simulating an acute abdomen and suggests that the differential diagnosis with a true surgical condition may be achieved by the observation of the progression of symptoms and by early evaluation of patient with EEG.

[Partial trisomy 9q: description of a new case]. / Trisomia parziale 9q: descrizione di un nuovo caso.

The authors describe one case of partial 9q trisomy they observed. The malformations they observed are correspondent to the very little amount of existing documented cases. And just because we have only a few observations, we thought useful publishing this case, to better define the clinical features among the alterations of chromosome 9 (trisomy 9 p and 9q). Head, neck, bones, heart and urogenital apparatus seen to be the most frequently involved in the phenotypic expression of the 9q trisomy.