Distribution of killer cell immunoglobulin-like receptors genes in the Italian Caucasian population.

BACKGROUND: Killer cell immunoglobulin-like receptors (KIRs) are a family of inhibitory and activatory receptors that are expressed by most natural killer (NK) cells. The KIR gene family is polymorphic: genomic diversity is achieved through differences in gene content and allelic polymorphism. The number of KIR loci has been reported to vary among individuals, resulting in different KIR haplotypes. In this study we report the genotypic structure of KIRs in 217 unrelated healthy Italian individuals from 22 immunogenetics laboratories, located in the northern, central and southern regions of Italy. METHODS: Two hundred and seventeen DNA samples were studied by a low resolution PCR-SSP kit designed to identify all KIR genes. RESULTS: All 17 KIR genes were observed in the population with different frequencies than other Caucasian and non-Caucasian populations; framework genes KIR3DL3, KIR3DP1, KIR2DL4 and KIR3DL2 were present in all individuals. Sixty-five different profiles were found in this Italian population study. Haplotype A remains the most prevalent and genotype 1, with a frequency of 28.5%, is the most commonly observed in the Italian population. CONCLUSION: The Italian Caucasian population shows polymorphism of the KIR gene family like other Caucasian and non-Caucasian populations. Although 64 genotypes have been observed, genotype 1 remains the most frequent as already observed in other populations. Such knowledge of the KIR gene distribution in populations is very useful in the study of associations with diseases and in selection of donors for haploidentical bone marrow transplantation.

Hierarchy of baby-linked immunogenetic risk factors in the vertical transmission of hepatitis C virus.

Mother-to-infant transmission of Hepatitis C Virus (HCV) represents the major cause of pediatric HCV infection today. Immunogenetic influence has been poorly investigated and mainly confined to HLA-class II serological polymorphisms. Among 290 parities, 135 from Pavia and 155 from Bergamo, of HCV-RNA-infected Italian women, 21 babies (7.24%) were HCV-RNA positive at birth and steadily positive over 20 months of life. All the 21 infected babies and 44 randomly selected uninfected ones, born to HCV-RNA+ mothers but steadily negative for HCV-RNA during a follow-up of 2 years, and their mothers were investigated for HLA-G, -C, -DRB1, -DQA1 and -DQB1 genomic polymorphisms. Among the different covariates, HLA-Cw*07, -G*010401, -DRB1*0701, -DRB1*1401 and homozygosity for HLA-G 14bp deletion can be considered as risk factors for HCV vertical transmission. On the contrary, protection was conferred by the HLA-DQB1*06, -G*0105N, -Cw*0602, DRB1*1104 and -DRB1*1302 alleles. Our initial question was: has the immunogenetic profile any role in the protection of the fetus growing in an infected milieu and, if so, is it independent from the other non-immunogenetic parameters? The answer to both questions should be yes.

Helicobacter pylori infection and autoimmune thyroid disease in young patients: the disadvantage of carrying the human leukocyte antigen-DRB1*0301 allele.

CONTEXT AND OBJECTIVE: Pathogenesis of autoimmune thyroid disease (ATD) is multifactorial. Helicobacter pylori (Hp) infection has been proposed to be involved in nongastrointestinal conditions and reported more frequently in ATD adult patients. We evaluated the prevalence of Hp antibodies in young ATD patients and investigated the possibility that a susceptible immunogenetic profile could influence the development of ATD in subjects with Hp infection. SUBJECTS AND METHODS: We retrospectively studied 90 children with ATD (median age 11.2 yr), 70 age- and sex-matched healthy subjects as controls, and 65 patients with Turner syndrome (median age 18.8 yr). Antibodies to Hp were determined at diagnosis in ATD patients and, in Turner patients, at the last control in cases without ATD and before the appearance of thyroid autoantibodies in the others. Serological and molecular human leukocyte antigen (HLA) typing for classes I and II polymorphisms was performed. RESULTS: Prevalence of positive Hp serology resulted significantly higher in ATD patients than controls (P = 0.032). No association was found between individual HLA alleles and Hp serology. HLA-A1, B8, and DRB1*0301 were found significantly associated with ATD. A significant interaction between HLA-DRB1*0301 and Hp infection was present in ATD patients and not controls (P = 0.007), suggesting that the copresence of these two factors might favor ATD development. A similar phenomenon was observed in Turner syndrome patients (P = 0.02; cumulative Mantel test, P = 0.0001). CONCLUSIONS: Another target of Hp-elicited immune inflammatory response might be the thyroid gland in subjects with a peculiar immunogenetic profile so that ATD may be a consequence. Our findings suggest the opportunity of eradicating Hp infection in children with ATD and/or susceptible HLA alleles.

Donor-recipient incompatibility at CD31-codon 563 is a major risk factor for acute graft-versus-host disease after allogeneic bone marrow transplantation from a human leucocyte antigen-matched donor.

Disparities at minor histocompatibility antigens (mHA) are thought to be responsible for acute graft-versus-host disease (aGVHD) in patients receiving bone marrow transplantation (BMT) from a human leucocyte antigen (HLA)-matched donor. Although some mHA have been identified in humans, their role in aGVHD has not. Patients (n = 150) receiving a BMT from an HLA-matched donor were investigated for a correlation between aGVHD and donor/recipient incompatibility for seven polymorphisms previously proposed for mHA (HA-1, H-Y, CD31-codon 125, CD31-codon 563, HPA-1, HPA-3 and HPA-5). Only mismatch at CD31-codon 563 predicted grade II-IV aGVHD. The risk derived from CD31-codon 563 mismatch was the same as that derived from the use of bone marrow from an unrelated donor. We suggest that donor/recipient compatibility at CD31-codon 563 should be added to HLA-typing for donor selection and/or adjustment of aGVHD prophylaxis.

Acute promyelocytic leukemia toluidine blue subtype.

In the hypergranular group of acute promyelocytic leukemia (APL) a rare subvariant with basophilic granules, metachromatic for toluidine blue, is recognizable. To evaluate the incidence as well as the biological and clinical significance of this subtype, we studied 53 consecutive untreated patients with APL with morphological, cytochemical, immunological and cytogenetic methods. In 10 cases (19% of the total) granules stained metachromatically in percentages of promyelocytes ranging from 16 to 60. In these cases peroxidase positivity was weaker than in the classic hypergranular and microgranular M3 and activities of esterases were usually present; at the ultrastructural level granules contained particulate material. Immunophenotypic and cytogenetic characteristics seemed not to differ from those of other M3 cases. Coagulopathy was usually life-threatening, notwithstanding the low white cell count, and the median survival was short. Hyperhistaminemia-related symptoms were not observed. Cytochemical, immunologic and cytogenetic findings are useful to differentiate this form from M2 with basophilic differentiation and from mast cell leukemia.

Acute promyelocytic leukemia: morphological and clinical features.

BACKGROUND AND METHODS: Acute promyelocytic leukemia (APL) is not a morphologically homogeneous entity: to verify whether there is any relationship between this heterogeneity and other biological and clinical aspects, we studied 43 cases of APL with morphological, cytochemical, cytogenetic and immunological methods. RESULTS: Three morphological categories were present: a classic hypergranular type (30 cases), a microgranular type (6 cases) and a form with basophilic granules (M3b) that stained metachromatically with toluidine blue (7 cases). In all these groups there were cases with cytochemical features of both myeloid and monocytic type (alpha-naphthyl-acetate esterase positive). No immunological and cytogenetic differences were observed; the morphological variant with basophilic granules was more frequent in females; age distribution was not related to the morphological subtype; organomegaly was extremely rare in M3b. A low white blood cell count was constant in M3b, whereas no differences were observed in hemoglobin and platelet values. Severity of bleeding was worst in the group with toluidine blue metachromasia; this and the microgranular type had poor prognosis. CONCLUSIONS: Our study confirms the importance of identifying different cytologic categories in APL. In particular we focused our attention on a new variant with basophilic granules.

Transient aplasia preceding adult acute lymphoblastic leukemia.

A 62-year-old woman developed common acute lymphoblastic leukemia (ALL) after spontaneous recovery from transient marrow aplasia. Although the mechanisms underlying bone marrow suppression in acute leukemia are obscure, it is important to know that transient aplasia may be observed as a prodromal feature in ALL in adult patients as well as in children.

Immunocytochemical detection of factor XIII A--subunit in acute leukemia.

Factor XIII (FXIII) is a plasma pro-transglutaminase consisting of A and B subunits in a tetrameric structure. A cellular form of FXIII consisting exclusively of A subunits exists in platelets and monocytes: monocyte FXIII may be involved in connective tissue organization. To evaluate the expression and diagnostic significance of FXIII A subunit (FXIIIA) in acute leukemia, we performed an immunocytochemical study (PAP technique) with rabbit antiserum against FXIIIA on leukemic blasts of 48 cases. FXIIIA was detected only in myelomonocytic (M4), monocytic (M5) and megakaryocytic (M7) cases: in M4 and M5 samples the amount of blast cytoplasmic FXIIIA was closely correlated with the expression of monocyte-specific antigenic and cytochemical markers. Our data show immunocytochemical detection of FXIIIA to be useful for acute leukemia characterization.

Arteriovenous fistula between the hepatic artery and the hepatic vein.

A patient is presented with multiple vascular anomalies in the branches of the celiac axis as well as in the portal vein and its branches. Apparently, unique in the literature is the presence of a large arteriovenous fistula between the hepatic artery and one of the hepatic veins. The anomalies are presumed to be congenital in origin.

Possible role of collagen in transverse myelitis and chymopapain-induced paraplegia.

We studied the effect of nucleus pulposus (NP) on platelet aggregation. Our in vitro experiments showed that NP extract produced platelet aggregation and the addition of collagenase to the NP extract abolished this response. It was further shown that chymopapain did not affect the activity of the extract. We assume that collagen is the active platelet aggregant in the NP extract. Intravascular release of collagen may cause platelet aggregation, vascular obstruction, ischemia, and cord necrosis in a patient with acute transverse myelitis. Intradiskal chymopapain is known to cause transverse myelitis and it is possible that collagen released during the action of the enzyme initiates a similar chain of events.

Nail-patella syndrome. A distinctive clinical and electron microscopic presentation.

A case of nail-patella syndrome is presented in which cerebral vessel and aortic dilatation was noted. The skin revealed epidermal basement membrane thickening and redundancy in addition to significant perivascular basal lamina reduplication by electron microscopy. The significance of these findings is discussed.