Is the Pentagon-Copying Task More than a Cognitive Feature? Associations with Handgrip Strength, Gait Speed, and Frailty in Older Adults.

BACKGROUND: The pentagon copy is a sensitive item to the prediction of cognitive decline and dementia. Cognitive and physical/motor decline are able to accelerate the evolution of each other by representing a common pathway toward frailty. OBJECTIVES: The objective of the study was to investigate the association of the pentagon-copying task with physical and motor performances and with frailty, in a sample of older adults. METHOD: This observational, cross-sectional, and single-center study was conducted in a Geriatric Outpatients Clinic. Subjects aged ≥65 years were consecutively recruited, on a voluntary basis. Subjects with positive psychiatric history, with a severe neurocognitive disorder, with severe limitations on the upper limbs and/or reporting sensory deficits were excluded. The pentagon-copying task was scored from the Mini-Mental State Examination; the Qualitative Scoring Pentagon Test (QSPT) was also used. Handgrip strength was measured; a 46-item Frailty Index was calculated; in subjects with autonomous walking, a 4-meter gait speed was also measured. RESULTS: The study included 253 subjects (mean age 80.59 ± 6.89 years). Subjects making a wrong pentagon copy showed greater odds of exhibiting a strength deficit (OR = 3.57; p = 0.001) and of being frail (OR = 4.80; p < 0.001), and exhibited a slower gait. The QSTP score was significantly correlated with handgrip strength (r = 0.388) and gait speed (r = 0.188) and inversely correlated with frailty (r = -0.428); the QSTP score was significantly different between the quartiles of handgrip strength and frailty. CONCLUSIONS: The pentagon-copying task might also be confirmed as a quick screening tool of aging trajectories toward frailty by jointly evaluating cognitive and physical performances.

Emergence of exhausted B cells in asymptomatic HIV-1-infected patients naïve for HAART is related to reduced immune surveillance.

Alterations of B cell subpopulations have been described up to date as characterizing advanced stage of HIV-1 infection. However, whether such defects are relevant in subjects with a preserved number of CD4⁺ T cells (>350 cells/µL) is unclear. In a cross-sectional study, we investigated if signs of B cells exhaustion and impaired viral immune surveillance are present in a cohort of 43 asymptomatic HIV-1-infected patients with preserved CD4⁺ T cell counts (>350 cells/µL) and highly active antiretroviral therapy (HAART) untreated. A dramatic expansion of exhausted tissue-like memory B cells (CD10⁻CD21(low)CD27⁻) was observed. B cells alteration was related to an increase in Torque teno virus (TTV) load, used as surrogate marker of immune function. Successfully HAART-treated patients showed normalization of B cell subpopulations frequency and TTV load. These results provide new insights on B cell in HIV-1 infection and show that development of B cell abnormalities precedes CD4⁺ T cell decline.

The number of circulating recent thymic emigrants is severely reduced 1 year after a single dose of alemtuzumab in renal transplant recipients.

To better understand the kinetics of the delayed reconstitution of peripheral CD4+ T-cells after depletion with a single administration of alemtuzumab (AL) for renal transplantation, we evaluated in these patients the percentage and absolute number of recent thymic emigrants (RTEs) CD4+ T cells, together with naive and memory subsets, defined by the analysis of CD31, CD45RA and CCR7 expression, and compared with patients treated with a nondepleting protocol based on basiliximab, and with healthy controls. In AL-treated patients, the number of circulating CD4+ T cells was greatly reduced 1 year after the infusion (P < 0.01), but the proportions of central memory, effector memory and terminally differentiated effector memory subsets among CD4+ cells were significantly increased. On the contrary, the proportion and the absolute number of naïve CD4+ T cells, although progressively increasing with time, were severely reduced. In particular, the absolute number of RTEs had only very slight increase with time (P = 0.049) and was dramatically low 1 year after the therapy (P < 0.01 vs. healthy controls; P < 0.05 vs. basiliximab-treated transplant recipients). These data suggest that a prolonged defective thymic output after AL therapy in renal transplant recipients is one of the main causes of the persistent CD4+ T-cell lymphopenia observed in these patients.

Anti-cardiolipin and anti-beta2-glycoprotein I antibodies: performance of new commercial ELISA kits.

Antiphospholipid antibodies (aPL) are known to be pathogenic in experimental models and are predictive of thrombosis and miscarriages in patients, so it is important to correctly evaluate their presence for identifying patients at risk. Despite many years of work, the standardization of aPL ELISA remains an open problem, so evaluation of newly introduced commercial preparations is mandatory. A total of 80 sera were collected (10 primary antiphospholipid syndromes (APSs), 10 APSs associated with systemic lupus erythematosus, 20 infectious diseases, 20 rheumatoid arthritis and 20 normal blood donors) and tested for IgG/IgM anti-cardiolipin and anti-beta2GPI antibodies on commercial ELISA kits (ETI) by DiaSorin and on home-made ELISA. Both methods displayed good sensitivity and specificity for APS and were found to be concordant, especially in determining antibodies of IgG class.

Reduced thymic output, increased spontaneous apoptosis and oligoclonal B cells in polyethylene glycol-adenosine deaminase-treated patients.

Impairment of purine metabolism due to adenosine deaminase (ADA) deficiency is associated with a severe combined immunodeficiency (SCID). Polyethylene glycol-modified ADA (PEG-ADA) has provided noncurative, life-saving treatment for these patients, but full immune recovery is not achieved with this therapy. Since ADA-SCID is perhaps the most difficult form of SCID to handle clinically, understanding the benefits and limitations of PEG-ADA therapy may be relevant for treatment selection. To this purpose, we analyzed the rate of thymic output, T and B cell repertoires, number of T cell divisions, IFN-gamma and IL-4 production, and the extent of cell death in five ADA-SCID patients following a prolonged period of treatment with PEG-ADA. We found that thymic output was low in these patients. However, their T cell repertoire was heterogeneous, and their T lymphocytes produced cytokines upon activation and responded to mitogen stimulation, although with different kinetics. Furthermore, a high number of peripheral T lymphocytes were committed to apoptosis. Anomalies were also observed in the B cell compartment, with oligoclonal expansions of B cell clonotypes in two patients. Our data indicate that decreased thymic function, B cell oligoclonality, and increased spontaneous apoptosis may be the mechanisms by which the immunodeficiency of ADA-SCID patients persists in spite of treatment with PEG-ADA.

High prevalence of SEN virus infection in patients on maintenance hemodialysis: frequent mixed infections with different variants and evidence for nosocomial transmission of the virus.

OBJECTIVE: The SEN virus (SENV) represents a recently described group of DNA viruses, two members of which (SENV-D and SENV-H) are linked with posttransfusion hepatitis. Since patients on hemodialysis have a high risk of being infected by blood-borne viruses, we investigated the prevalence of seven SENV isolates in two distinct units of our hospital. METHODS: The presence of SENV was investigated in 171 hemodialysis patients and in 163 controls by using a polymerase chain reaction based methodology, with which the specificity of amplified products was detected by hybridization with probes specific for each variant. Polymerase chain reaction products from 4 patients were sequenced. RESULTS: The overall detection of SENV DNA as well as of SENV-D, SENV-E, and SENV-G was significantly higher in one of the two units, and there was a higher degree of homology in the sequences prepared from patients of the same unit. Furthermore, we demonstrated that mixed infections with multiple SENV were common. No relationship was observed between presence of SENV and sex, age, duration of hemodialysis, previous transfusions or transplantation, hepatitis infection, and routine liver test results. CONCLUSION: Our results indicate that patients who undergo hemodialysis can be at high risk of SENV transmission and suggest an intraunit transmission of specific SENV variants.

Reconstitution of T-cell compartment after in utero stem cell transplantation: analysis of T-cell repertoire and thymic output.

BACKGROUND AND OBJECTIVES: In utero transplantation of hematopoietic stem cells allows immune reconstitution of fetuses with severe combined immunodeficiency. The objective of this work was to study the quality of T-cell reconstitution following this procedure. DESIGN AND METHODS: We evaluated the kinetics and extent of T-cell reconstitution in five infants with severe combined immune deficiency (SCID), three with a B+ and two with a B- phenotype, who received haploidentical stem cell transplantation before birth. To this end, we measured the frequency of T-cell receptor excision circles (TREC) and the diversity of the T-cell repertoire. RESULTS: In utero transplantation led to engraftment of donor-derived T lymphocytes which attained normal numbers in four infants, who are in good health. In the three patients with a B+ phenotype, generation of a heterogeneous T-cell repertoire was associated with development of TREC levels comparable to those of SCID patients treated by post-natal transplantation and of healthy babies. Of the two patients with a B- phenotype, one developed mixed T-cell chimerism and a substantial number of circulating T cells, associated with a variable heterogeneity of the T-cell repertoire; TREC levels were normal soon after birth, but declined thereafter. The remaining B- patient remained lymphopenic with a skewed T-cell repertoire and very low TREC levels. This patient eventually required transplantation from a matched unrelated donor at 5 years of age, but died of EBV-related lymphoproliferative disease. INTERPRETATION AND CONCLUSIONS: These data indicate that in utero transplantation of fetuses with B+ SCID allows generation of newly diversified T lymphocytes and ensures long-term reconstitution of cell-mediated immunity.

Effect of HAART on SEN virus infected HIV positive patients.

Since it has been demonstrated that concomitant infections could influence the outcome of antiviral treatment, we investigated whether the presence of SENV infection may interfere with highly active antiretroviral therapy (HAART) in HIV+ coinfected patients. In spite of persistent fluctuations in SENV-A positivity we could not find any correlation between SENV-DNA and the immunological and virologic parameters found in the patients, suggesting SENV has no apparent clinical relevance during highly active antiretroviral therapy.

Tracking the source of the hepatitis B virus-specific CD8 T cells during lamivudine treatment.

Lamivudine treatment in chronic hepatitis B leads to the reconstitution of virus-specific T cells in the circulation, but it is not clear whether this is the preferential result of T cell efflux from the liver or lymph nodes. To address this question, the frequency and function of liver-, lymph node-, and blood-derived hepatitis B virus (HBV)-specific CD8 T cells were analyzed in patients treated with lamivudine and undergoing liver transplantation. HBV-specific CD8 T cells, identified in portal lymph nodes, were able to expand in vitro after antigen-specific stimulation and displayed a heterogeneous profile of cytokine production. These findings suggest that the peripherally reconstituted HBV-specific CD8 T cells can originate from precursor cells within lymph nodes.