Soluble HLA-A,-B,-C and -G molecules induce apoptosis in T and NK CD8+ cells and inhibit cytotoxic T cell activity through CD8 ligation

There is convincing evidence that soluble HLA-A,-B,-C (sHLA-A,-B,-C) and soluble HLA-G (sHLA-G) antigens can induce apoptosis in CD8(+) activated T cells although there is scanty and conflicting information about the mechanism(s) by which sHLA-A,-B,-C antigens and sHLA-G antigens induce apoptosis. In this study we have compared the apoptosis-inducing ability of sHLA-A,-B,-C antigens with that of sHLA-G1 antigens in CD8(+) T lymphocytes and CD8(+) NK cells. Furthermore we have compared the inhibitory effect of sHLA-A,-B,-C antigens and of sHLA-G1 antigens on the activity of EBV-specific CD8(+) cytotoxic T lymphocytes (CTL). sHLA molecules were purified from serum and from the supernatant of HLA class I-negative cells transfected with one gene encoding either classical or non-classical HLA class I antigens. Both classical and non-classical sHLA class I molecules trigger apoptosis in CD8(+) T lymphocytes and in CD8(+) NK cells, which lack the T cell receptor, and their apoptotic potency is comparable. The binding of sHLA-A,-B,-C and sHLA-G1 molecules to CD8 leads to Fas ligand (FasL) up-regulation, soluble FasL (sFasL) secretion and CD8(+) cell apoptosis by Fas/sFasL interaction. Moreover, classical and non-classical sHLA class I molecules inhibit the cytotoxic activity of EBV-specific CD8(+) CTL. As the amount ofsHLA-G molecules detectable in normal serum is significantly lower than that of sHLA-A,-B,-C molecules, the immunomodulatory effects of sHLA class I molecules purified from serum are likely to be mainly attributable to classical HLA class I antigens. As far as the potential in vivo relevance of these findings is concerned, we suggest that classical sHLA class I molecules may play a major immunoregulatory role in clinical situations characterized by activation of the immune system and elevated sHLA-A,-B,-C serum levels. In contrast, non-classical HLA class I molecules may exert immunomodulatory effects in particular conditions characterized by elevated sHLA-G levels such as pregnancy and some neoplastic diseases.     

Kif1Bbeta isoform is enriched in motor neurons but does not change in a mouse model of amyotrophic lateral sclerosis

The kinesin superfamily motor protein Kif1B is expressed in two isoforms, Kif1Balpha and Kif1Bbeta, with distinct cargo-binding domains. We examined the mRNA distribution of the two isoforms in adjacent sections of brain and spinal cord of adult mice using in situ hybridization analysis. Kif1Bbeta mRNA is enriched in several regions of brain and spinal cord. Its levels are four to five times higher than that of the alpha isoform, which was barely detectable. The highest mRNA levels of Kif1Bbeta were found in the cortex, hippocampus, cerebellum and the grey matter of the spinal cord. At the cellular level the highest signal was found in motor neurons in the motor nuclei of medulla oblongata and the ventral horn of spinal cord. Because expression of other Kif genes is altered in amyotrophic lateral sclerosis (ALS) models, we examined the expression level of Kif1Bbeta mRNA in the spinal cord of transgenic mice carrying the SOD1G93A mutation, a model of familial ALS, at presymptomatic and early stages of the disease. No changes were observed in Kif1Bbeta mRNA in motor neurons or in other regions of the spinal cord. These findings indicate that Kif1Balpha, which modulates the transport of mitochondria, may play a major role in tissues other than the central nervous system. Instead Kif1Bbeta, responsible for the transport of synaptic vesicle precursors, seems to play an important role in the nervous system, particularly in the lower motor neurons. The absence of changes of Kif1Bbeta mRNA in transgenic SOD1G93A mice suggests that other molecular mechanisms may play a role in the disruption of axonal transport occurring in the motor neurons of these mice.     

Sex and gender approach for precision rheumatology

Clinical Rheumatology -     

Neurovascular Neck-Bridging device in treatment of wide-necked splenic artery aneurysms

We report the cases of 2 female patients, 45-year-old and 49-year-old, affected by wide-necked splenic aneurysm. We embolized the 2 lesions assisted by a new scaffolding neurovascular device, the Cascade Net, an innovative –occlusive remodeling device for temporary bridging in endovascular coil embolization of intracranial aneurysms. Visceral artery aneurysms are rare with an estimated prevalence of 2%-3% in imaging series and up to 10% in autopsy series. Most are asymptomatic and their diagnosis is occasionally. Aneurysm spontaneous rupture has been demonstrated in 2%-10% of cases and it can result in significant morbidity and mortality. Conservative management and open repair were the preferred treatment options for many years. Endovascular repair has been increasingly used since 2000; and the most widespread method of treatment has been coiling. Because of tortuosity of the parent artery, wide neck, and unfavorable locations at arterial branch points, 6% of Visceral and renal artery aneurysms VRAA cannot be adequately treated by simple coiling and requires parent artery remodeling through balloon occlusion, stent placement or parent vessel occlusion, leading to, in the latter situation, a compromised organ perfusion. Increasingly, balloon-assisted, and stent-assisted approaches as well as novel scaffolding neurovascular devices such as the Cascade Net, have allowed wide necked aneurysms to be bridged during endovascular treatment with smaller delivery system, averting parent artery occlusion and risk of distal embolization.     

The Anti-SARS-CoV-2 Antibody Response in a Centenarian Woman: A Case of Long-Term Memory?

SARS-CoV-2 is the virus responsible for the COVID-19 pandemic, causing respiratory syndrome and other manifestations. The clinical consequences of the SARS-CoV-2 infection are highly heterogeneous, ranging from asymptomatic and mild to severe and fatal conditions, with the highest mortality rate reached among elderly people. Such heterogeneity appears strongly influenced by the host immune response, which in turn is profoundly affected by aging. In fact, the occurrence of a low-grade inflammation and a decline in specific immune defense is generally reported in older people. Although the low ability of B cells to provide primary and secondary specific responses with a consequent increase in susceptibility to and severity of virus infections is generally described in elderly people, we would like to present here the particular case of a 100-year-old woman, who recovered well from COVID-19 and developed a long-term memory against SARS-CoV-2. Following the infection, the patient’s blood was tested with both a classical ELISA and a specific Cell-ELISA addressed to measure the anti-spike S1 specific IgG released in plasma or produced in vitro by memory B cells, respectively. While showing negative on classical serological testing, the patient’s blood was positive in Cell-ELISA up to 1 year after the infection. Our observation highlights a potential mechanism of B cell-dependent, long-term protection in response to SARS-CoV-2 infection, suggesting that in a case of successful aging, the absence of specific antibodies in serum does not necessarily mean the absence of immune memory.