HLA and MICA polymorphism in Polynesians and New Zealand Maori: implications for ancestry and health.

Data from HLA typing studies have made significant contributions to genetic theories about the Austronesian diaspora and the health of descendant populations. To help further unravel pattern and process elements, we have typed HLA and MICA loci at high resolution in DNA samples from well defined groups of Maori and Polynesian individuals. Our results show a restricted set of HLA class I alleles compared with other well characterised populations. In contrast, the class II HLA-DRB1 locus seems to be diverse in Maori and Polynesians and both groups show high frequencies of HLA-DRB1(∗)04:03, -DRB1(∗)08:03, -DRB1(∗)09:01 and -DRB1(∗)12:01. Our survey also provides the first ever MICA datasets for Polynesians and reveal unusual distributions and associations with the HLA-B locus. Overall, our data provide further support for a hybrid origin for Maori and Polynesians. One novel feature of our study is the finding that the gene sequence of the HLA-B(∗)40:10 allele in Polynesians is a recombinant of HLA-B(∗)55:02 and -B(∗)40:01. HLA-B(∗)40:10 is in close association with HLA-C(∗)04:03, an allele identified as a hybrid of HLA-C(∗)04 and -C(∗)02. In this respect, our data resemble those reports on Amerindian tribes where inter-allele recombination has been a common means of generating diversity. However, we emphasize that Amerindian gene content per se is only a very minor element of the overall Polynesian genepool. The wider significance of HLA and MICA allele frequencies across the Pacific for modern day health is also discussed in terms of the frequency relative to reference populations of disease known to be associated with specific HLA and MICA markers. Thus, Polynesians and Maori are largely unaffected by "European autoimmune diseases" such as ankylosing spondylitis, uveitis and coeliacs disease, yet there are several Maori- and Polynesian-specific autoimmune diseases where the HLA and MICA associations are still to be determined.

LDL apheresis in the treatment of non-arteritic ischaemic optic neuropathy: a 6-month follow-up study.

PURPOSE: Verify the recovery of visual capacity after the administration of a combination of LDL apheresis (LA) and conventional therapy (CT). Design, prospective and interventional case series. METHODS: 20 patients affected by NAION were randomly subdivided into two groups of 10 patients (Group 1 and Group 2). Group 1 underwent three sessions of LA associated with CT, whereas group 2 received only CT. At discharge and at the 6 months follow-up visit, assessment in both groups was made of the best corrected visual acuity (BCVA) and the computerised visual field (CVF), comparing the findings with those at admission in each patient. RESULTS: Only the mean deviation (MD) at CVF was statistically improved in group 1 as compared with group 2 at discharge, judged against the values at admission (-11.08+/-6.51 vs -16.53+/-10.03, P=0.039; -17+/-5.24 vs -14.14+/-9.42, respectively). However, this increase was not confirmed at 6 months (-16.83+/- -10.72, group 1; -13.56+/-3.60 group 2). CONCLUSION: In NAION, LA induced a short term improvement in the MD, but by 6 months this had disappeared.

Double-filtration plasmapheresis in the treatment of leg ulcers in cryoglobulinemia.

Hepatitis C virus (HCV) is the major cause of cryoglobulinemia. Skin lesions are frequent and can be cured from the removal of cryoglobulins by therapeutic apheresis. We describe a case of HCV-positive type I cryoglobulinemia with severe leg ulcers, not responsive to antiviral and immunosuppressive treatment. Thirty sessions of double filtration plasmapheresis were performed, over a period of 6 months, with no other associated treatment. Before and after each session an assessment of immunoglobulins, complement, cryocrit, and fibrinogen was made. HCV RNA levels were determined in serum cryoprecipitate, supernatant before and after each session, and in the collection bag. No differences in pre and postapheresis values were observed in the serum concentrations and the supernatant, whereas the postapheresis cryoprecipitate showed a significantly reduced viral load (P < 0.02) as compared with the preapheresis values. There was improvement in the condition of ulcers in the leg during apheresis and had completely regressed by the end of the cycle.

Fibrinogen apheresis in the treatment of peripheral arterial disease.

BACKGROUND: Fibrinogen is mainly responsible for determining the viscosity of whole blood. In peripheral arterial disease (PAD) the fibrinogen concentration seems to affect the microcirculation flow. AIM: To study the effects of an abrupt reduction of fibrinogen on the hemodynamics of the lower extremities and the clinical picture of patients with PAD. METHODS: Ten patients affected by various stages of PAD underwent 1 session of fibrinogen apheresis (TheraSorb, Miltenyi Biotec, Germany). Laboratory parameters of endothelial activation were assessed before and after the session, as well as walking distance (WD), the ankle-brachial index and laser Doppler flowmetry. RESULTS: A significant reduction in the laboratory parameters was observed: fibrinogen (50%), total cholesterol (18%), LDL cholesterol (24%), sE-selectin (23%), sICAM-1 (19%) and sVCAM-1 (10%). The procoagulant factors, factor VIII and von Willebrand factor, did not vary significantly. Both pain-free and total WD were significantly improved (p < 0.003 and p <0.006, respectively), the ankle-brachial index remained unchanged, and laser Doppler flowmetry showed a modest but not significant increase. CONCLUSIONS: Fibrinogen apheresis allowed us to study the effects of an acute modification of fibrinogen in PAD, on both some aspects of the endothelial function and on the hemodynamics, demonstrating an improvement of WD and a minimal increase in the skin microcirculation.