Systemic lupus erythematosus occurring in a patient with Niemann-Pick type B disease.

Niemann-Pick disease is an inherited lipid storage disorder caused by the deficiency of acid sphingomyelinase, which results in accumulation of sphingomyelin within cells of several organs and consequent tissue damage. The broad clinical spectrum of this disorder may overlap with that of systemic lupus erythematosus, hindering differential diagnosis. Herein, we report the case of a patient affected by Niemann-Pick type B disease intertwined with clinical and serological features of systemic lupus erythematosus. Two novel mutations in the SMPD1 gene were found in compound heterozygosity: p.A36V and IVS2 + 8 T > G.

Switch to icatibant in a patient affected by hereditary angioedema with high disease activity: a case report.

Icatibant, an antagonist of the bradykinin B2 receptor, was approved for the treatment of acute attacks of hereditary angioedema in the EU in 2008. This paper presents the case of a 65-year-old woman affected by frequent acute attacks of hereditary angioedema who benefitted from a change of therapy to icatibant, following years of treatment with C1-inhibitor.

An uncommon association of antiphospholipid syndrome, selective IgA deficiency and resistant-to-treatment relapsing polychondritis: efficacy of infliximab.

Autoimmune complications in the context of primary immunodeficiency diseases represent a well-known phenomenon, and this is widely recognized also for Selective Immunoglobulin A deficiency (IgAD), the most common primary antibody deficiency (PAD). Relapsing polychondritis (RP) is a rare immune-mediated, difficult to treat, disorder in which the cartilaginous tissues are the target for inflammation and damage. Ocular inflammatory manifestations in RP are frequent and often sight-threatening. Antiphospholipid syndrome (APS) is an acquired prothrombotic state related to circulating autoantibodies against phospholipids and/or their cofactors. Rare reports of APS associated to RP, PAD and APS or PAD and RP are available.

Raltegravir, tenofovir, and emtricitabine in an HIV-infected patient with HCV chronic hepatitis, NNRTI intolerance and protease inhibitors-induced severe liver toxicity.

BACKGROUND: In HIV-infected patients with HCV-related chronic hepatitis, liver impairment and drug toxicity may substantially reduce the number of possible therapeutic options. CASE DESCRIPTION: we here describe the case of an HCV-HIV coinfected woman who had repeated severe episodes of drug-related liver toxicity with indinavir, saquinavir, fosamprenavir, and darunavir, with minimal further therapeutic options left in this class. Previous treatment-limiting side effects with efavirenz and nevirapine also precluded use of non-nucleoside reverse transcriptase inhibitors. Introduction of an integrase-inhibitor regimen based on raltegravir, tenofovir, and emtricitabine allowed a prompt achievement of undetectable viral load and a substantial rise of CD4 count to high levels, with no subsequent episodes of hepatic toxicity, and no other side effects. CONCLUSIONS: given the relatively common prevalence of HCV-related chronic hepatitis among people with HIV, raltegravir might represent an important alternative option for a substantial number of patients who cannot be treated with protease inhibitors or NNRTI because of drug-related hepatic toxicity.

Surface markers on lymphocytes from human cerebrospinal fluid. Identification by monoclonal antibodies.

Lymphocyte subpopulations in cerebrospinal fluid (CSF) and peripheral blood (PB) were studied using monoclonal antibodies and the common membrane markers. The results in three groups of patients were compared: 36 subjects with 'non-immunological disorders' (NID), 14 subjects with multiple sclerosis (MS) and 6 with subacute sclerosing panencephalitis (SSPE). It was found that, in patients with NID, (1) 90% of cells were T lymphocytes, reactive with OKT3; (2) the helper/suppressor (T4/T8) ratios were the same in the CSF and the PB; (3) the OKIa1 percentage was lower in the CSF than in the PB; and (4) only a few cells were 'immature', reacting with OKT10. Using the membrane markers (E rosettes, Fc IgG receptors and surface immunoglobulins), on the other hand, it was noted that the majority of cells in the CSF were identified as suppressor T lymphocytes and surface immunoglobulin-positive B cells were less common than the Ia1 marker suggested. There were no significant differences between the CSF results in patients with NID and MS but the OKT3 lymphocytes were reduced in CSF samples from patients with SSPE.

Lymphocyte subsets in human adenoids and tonsils. Rosette formation, alpha-naphthyl acetate esterase cytochemistry, monoclonal antibodies and peanut lectin reactivity.

The distribution of mononuclear cell subsets has been studied in human adenoids, tonsils and peripheral blood (PB) by evaluating the presence of surface immunoglobulins, E-rosette formation, receptors for IgG Fc and for complement, alpha-naphthyl acetate esterase (ANAE) cytochemistry, reactivity with peanut lectin (PNA) and with monoclonal antibodies (McAb) (OK panel). Adenoids and tonsils, compared to PB, contain (1) fewer macrophages and T cells but more B cells; (2) higher proportions of ANAE negative, complement receptors and Ia-like antigens bearing T lymphocytes; (3) higher percentages of cells reacting with the McAbs OKT9 and OKT10 ("immature" lymphoid cells). In both adenoids and tonsils, clusters, formed by a central heavily ANAE stained interdigitating cell surrounded by lymphocytes with a sickle-shaped ANAE reaction, were found. Analogous clusters have been previously described in mice and human thymus. Two major hypotheses could be put forward: (1) adenoids and tonsils contain "immature" lymphoid cells undergoing education process, or (2) the above organs contain lymphocytes activated by a constant exposure to bacterial antigens or mitogens.

Antigenic and cytochemical characterization of cells adhering to intrauterine contraceptive devices.

Eighteen copper intrauterine devices (IUDs), removed after 25 months of use, were examined to evaluate cells adhering to them (IAC). By means of monoclonal antibodies, the antigenic phenotype of IAC was studied, along with some IAC cytochemical properties. Sixty percent of IAC were identified as granulocytes based on morphological, cytochemical, and antigenic characteristics. A small proportion of IAC were shaped like large foreign-body macrophages, with multiple picnotic nuclei, and diffused alpha naphthyl acetate esterase (ANAE) activity. Some IAC identified as macrophages from a morphological view point also showed dipeptidyl-diaminopeptidase IV (DAPIV) reactivity, previously described only in T-helper lymphocytes. Most IAC identified as macrophages reacted with the monoclonal antibodies OKM1 and HLA-DR, and showed ANAE activity in the form of small multiple granules. The hypothesis that IUD-adhering macrophages with an ANAE+, DAPIV+, OKM1+, and HLA-DR+ phenotype could play a role in the inactivation of spermatozoa can be proposed.

Primary HIV-1 resistance in recently and chronically infected individuals of the Italian Cohort Naive for Antiretrovirals.

The risk of acquiring HIV-1 drug resistance at time of infection has become a public health problem following the widespread use of antiretroviral drugs in developed countries. Although a number of studies have reported data regarding the prevalence of HIV-1 primary resistance in developed countries over the past years, limited knowledge is available regarding the proportion of mutations related to drug resistance in antiretroviral naive subjects with chronic HIV-1 disease. In this study, we evaluated the prevalence of mutations in the reverse-transcriptase (RT) and protease region both in a representative group of recently HIV-1 infected subjects (n=68) and a cohort of chronically-infected HIV-positive patients (n=347) enrolled in the Italian Cohort of Antiretroviral Naive patients (I.CO.NA.). In recently infected individuals, the overall prevalence of mutations for nucleoside RTI (NRTIs) was 10/68 (14.7%). The distribution of mutations by calendar year were 0, 1 in 1996, 9, 3 in 1997 and 1, 0 in 1998 for NRTIs and protease inhibitors (PIs) respectively. Thymidine associated mutations were identified in six subjects (8.8%), five of whom had one mutation [41L, 70K (n=2), 215Y] and one had two mutations (67N+219Q). Four subjects (5.9%) showed the changes associated with resistance to lamivudine (184V or 118I). No non nucleoside-RTI (NNRTI) mutations were present in the study period. Primary PIs mutations (two 46L and two 82I) were present in four subjects (5.9%). Of note, mutations related to resistance to more than one class of antiretrovirals were present in one (1.5%). Among patients with chronic infection a large proportion (88.5%) carried no mutations in RT region, 11.5% individuals carried one or more mutations associated with resistance to NRTI (7.8%), or NNRTI (4.9%), with 4 patients carrying mutations to both classes. Among mutations associated with high-level resistance to RTI, T215Y was found in only 2 patients, M184V in 2 cases, T69D in another case, and K103N in only 1 patient, for a total of 6 patients (one carrying both T215Y and M184V) (1.7%). Primary mutations associated with substantial resistance to PIs were found in only 5/347 patients (1.4%); all the other patients carried only secondary mutations. Prevalence of mutations associated with high-level resistance to antiretroviral drugs is stable in recently infected individuals and low in patients with established HIV infection. The potential impact of transmitted mutations on the response to first regimen in individuals carrying transmitted mutations needs to be assessed by prospective studies.

Lymph node immunohistology in intravenous drug abusers with persistent generalized lymphadenopathy.

Lymph node biopsy specimens from 16 intravenous drug abusers with persistent generalized lymphadenopathy were evaluated by immunohistochemical methods using a panel of antisera to detect different cell populations. The 11 cases that we tested on cryostat sections showed an increased number of Leu-2a-positive cells (cytotoxic-suppressor phenotype) in the follicular centers and a significantly reduced helper-to-suppressor T-cell mean ratio when compared with control tissues. In these 11 patients the peripheral helper-suppressor ratio was at the lower normal limit or inverted. Ten cases tested for anti-human T-cell lymphotropic virus type III antibodies were positive. In all 16 cases, immunohistology of paraffin-embedded sections demonstrated a polyclonal B population; 12 of 15 patients tested had polyclonal hypergammaglobulinemia, mostly IgG. The mixed-cell population of the lymph node sinuses was composed mostly of Leu-M1-positive and lysozyme-positive cells and, to a lesser extent, by alpha 1-antichymotrypsin-positive and S100 protein-positive cells. It seems that many of the immunologic dysfunctions found in these patients appear to be reflected in a fairly repetitive immunohistologic pattern.

[Effects of Hodgkin cytotoxic serum on electrophoretic mobility of normal and Hodgkin peripheral blood lymphocytes. (author's transl)]. / Effetto del siero citotossico di pazienti con malattia di Hodgkin sulla mobilità elettroforetica di linfociti periferici normali e hodgkiniani

The effect of Hodgkin patient cytotoxic sera on the electrophoretic mobility of normal and Hodgkin peripheral blood allo-lymphocytes has been studied. Contact with cytotoxic serum determined a significant decrease in the electrophoretic mobility of lymphocytes, due to the presence of cytotoxic antibody on the lymphocyte surface. The antibody seems to be directed against T-lymphocytes. The results are discussed in the light of the preceding data by the authors on the role of anti-T-autoantibodies in Hodgkin's disease.

[Effects of Hodgkin cytotoxic serum on blast transformation of normal and Hodgkin human peripheral blood lymphocytes]. / Effetto del siero citotossico di pazienti con malattia di Hodgkin sulla PHA-responsività in vitro di linfociti periferici umani

The PHA-resposiveness of normal and Hodgkin patient human peripheral blood lymphocytes has been studied before and after incubation with Hodgkin cytotoxic sera. The following conclusions have been reached: (a) Hodgkin cytotoxic serum is capable of decreasing the PHA-responsiveness of normal lymphocytes and of furtherly impairing the already defective PHA-responsiveness of Hodgkin lymphocytes. (b) The impaired PHA-responsiveness can be restored to the original levels by eluting the cytotoxic antibody. Control experiments in which normal and Hodgkin lymphocytes were put in contact with normal and Hodgkin non-cytotoxic serum showed no decrease of PHA-responsiveness. These data are in agreement with the hypothesis that the presence of serum cytotoxin is at least partly responsible for the immuno-incompetence of T-lymphocytes characteristic of Hodgkin's disease.

Virological failure at one year in triple-class experienced patients switching to raltegravir-based regimens is not predicted by baseline factors.

We evaluated rates and determinants of virological failure in triple-class experienced patients receiving raltegravir-based regimens from a national observational study over 48 weeks, defined by any one of the following: (1) no HIV-RNA suppression to undetectable levels (<50 copies/mL) during follow-up; (2) detectable viral load after obtaining undetectable levels; and (3) leaving the study before 48 weeks. Among 101 eligible patients, 26 (25.7%; 95% CI 17.2-34.2) had virological failure. No significant differences between patients with and without virological failure were observed for gender, age, route of transmission, baseline CD4/HIV-RNA, CDC group, hepatitis B or C co-infections, resistance (based on the last genotype available), type and number of concomitant drug classes, concomitant use of darunavir, atazanavir, etravirine, enfuvirtide or maraviroc, and health-related quality-of-life measures. A high rate of treatment response was observed. The analyses did not identify any baseline factor associated with failure, including resistance status. Even if we cannot exclude the presence of pre-existing minority resistant variants not captured by genotypic tests, the lack of baseline predictors of failure suggests the need to monitor patients closely during follow up for other factors, such as potential drug interactions and reduced levels of adherence, which may favour virological failure.

T lymphocytes bearing receptors for Fc of IgG in guinea pig peritoneal fluid. A model for human extrahaematic fluids.

Surface markers of lymphocytes from peritoneal fluid of the guinea pig are studied and compared with those of lymphocytes from thymus, peripheral blood and spleen. The great majority of peritoneal lymphocytes form rosettes with rabbit red cells and bear receptors for Fc of IgG (T Fc+ cells). Lymphocytes with these characteristics are poorly represented in blood, thymus and spleen. Guinea pig peritoneal lymphocytes can be compared, as far as surface markers are concerned, with lymphocytes from human cerebrospinal fluid and transudates.