Giovanni Maria Ferri

Neuropsychiatric lupus syndromes: relationship with antiphospholipid antibodies.

The authors assessed the prevalence of neuropsychiatric manifestations occurring in patients with systemic lupus erythematosus (NPSLE), according to the American College of Rheumatology standardized definitions for NPSLE, and evaluated the relationship between NPSLE and antiphospholipid antibodies. Sixty-one consecutive SLE patients were studied. Neuropsychiatric manifestations consistent with the diagnosis of NPSLE occurred in 44 (72%). Patients with NPSLE showed significantly higher levels of anticardiolipin antibodies.

Anti‐cardiolipin antibodies in autoimmune thyroid diseases

OBJECTIVE In recent years anti‐phospholipid antibodies have gained much attention since they are frequently associated with thrombosis, recurrent abortion, and thrombocytopenia. Besides disease‐specific autoantibodies, other autoantibodies reactive with both organ and non‐organ specific autoantigens have been found in patients with autoimmune thyroid diseases. Therefore the objective of this study was to evaluate the presence and significance of anti‐phospholipid antibodies in untreated patients with different forms of autoimmune thyroid diseases.

Expression of lactoferrin on human granulocytes: analysis with polyclonal and monoclonal antibodies

Lactoferrin (LF), an iron‐binding protein present in specific granules of neutrophils, is expressed on membrane after granulocyte activation. It may represent a target for anti‐neutrophil cytoplasmic antibodies (ANCA) in patients affected by some immunomediated diseases. We recently produced two MoAbs, AGM 2.29 and AGM 10.14, that recognize two spatially distant epitopes of human LF. In this study we perform a cytometric analysis in order to evaluate the expression of LF on the surface of granulocytes obtained from freshly drawn blood or after purification, in both the presence and absence of stimuli. Our results demonstrate that LF is not constitutively expressed on membrane of circulating neutrophils. After priming with phorbol myristate acetate (PMA) or tumour necrosis factor‐alpha (TNF‐α), an increased mean fluorescence intensity (MFI) was obtained on neutrophils stained with polyclonal anti‐LF antibodies and with AGM 2.29. The kinetics of LF expression during activation demonstrated a progressive increase in MFI within 45 min. No increase in MFI was documented when primed granulocytes were stained with MoAb AGM 10.14, thus indicating that the epitope recognized by AGM 10.14 is not exposed at the cell surface. Following membrane permeabilization, performed in order to analyse the binding of anti‐LF MoAbs to cytoplasmic LF, a marked increase in MFI was obtained by staining granulocytes with both anti‐LF MoAbs. Indirect immunofluorescence (IIF) analysis confirmed that AGM 2.29 and AGM 10.14 reacted with human granulocytes, showing a cytoplasmic pattern on formalin–acetone‐fixed neutrophils and a perinuclear one on ethanol‐fixed cells.

Coexpression of CD69 and HLADR activation markers on synovial fluid T lymphocytes of patients affected by rheumatoid arthritis: a three-colour cytometric analysis.

The aim of the present study was to evaluate the coexpression of very early (CD69), early (CD25) and late (HLADR) antigens and to analyse the mean fluorescence intensity (MFI) of such activation markers on synovial fluid (SF) and peripheral blood (PB) lymphocytes of patients affected by rheumatoid arthritis (RA) and other types of chronic synovitis (OCS). A three colour cytometric analysis was performed using a peridinin chlorophyll protein conjugated anti‐CD3 antibody in combination with fluorescein isothiocyanate or phycoerythrin labelled anti‐CD69, anti‐HLADR, anti‐CD25 monoclonal antibodies (mAbs). A T cell gating method was utilized, so that three sets of bivariant dot plot quadrant displays were obtained (CD69/HLADR, CD69/CD25, CD25/HLADR). A large percentage of SF T lymphocytes in RA showed the coexpression of very early and late activation antigens (CD3 + CD69 + HLADR +), whereas CD3 + CD69 + CD25 + bearing cells and CD3 + CD25 + HLADR + lymphocytes were only a small percentage. Similar results were obtained in patients with OCS, although to a lesser extent. No statistically significant differences in MFI of CD69 and HLADR positive SF T cells between RA and OCS were observed. The CD69 + CD25‐HLADR + T cell subset is the most commonly represented in the synovial environment, among those we have evaluated; this phenotype may be characteristic of chronic inflammatory arthritis.

Anti-lactoferrin antibodies in systemic lupus erythematosus : isotypes and clinical correlates

Lactoferrin (LF) is a multifunctional iron-binding protein present in several mucosal secretions as well as in secondary granules of polymorphonuclear leukocytes (PMN). Anti-LF antibodies, which belong to antineutrophil cytoplasmic antibodies (ANCA), have been described in several immunomediated diseases, including systemic lupus erythematosus (SLE), with conflicting results regarding either their prevalence or clinical associations. We studied the prevalence and isotype distribution of anti-LF and their association with clinical manifestations, disease activity, and other autoantibodies in 97 patients (83 women) affected by SLE. Anti-LF were detected by enzyme-linked immunosorbent assay. Disease activity was assessed using the Systemic Lupus Activity Measure (SLAM). Cutoff for antibody positivity was set at three standard deviations (SD) above the mean optical density obtained in sera from 34 healthy subjects. Positive sera were arbitrarily subdivided into low (from >3 to 5 SD), medium (from >5 to 10 SD), and high (>10 SD) positive. IgG, IgM, and IgA anti-LF were detected in 53, 18, and 14 patients, respectively. IgG1, IgG2, IgG3, and IgG4 anti-LF were demonstrated in 34, 10, 31, and 35 patients, respectively. IgG anti-LF at the medium/high level were found in 33 patients, correlated with disease activity (p=0.017), anti-dsDNA (0.04), and anticardiolipin antibodies (p=0.02) and were associated with Raynaud’s phenomenon (p=0.028), renal involvement (p=0.007), serositis (p=0.026), and history of thrombosis (p=0.006). Anti-LF of IgM, IgA, or IgG subclass isotypes showed no correlation with clinical and serological findings. Our results demonstrate that anti-LF are frequently present in patients affected by SLE. IgG anti-LF at the medium/high level are associated with some clinical manifestations and other autoantibodies. However, it remains to be established whether anti-LF play a specific pathogenic role.

Prevalencia de las infecciones de los virus A, B, C y E de la hepatitis en dos grupos de niños de nivel socioeconómico distinto de Santa Cruz, Bolivia

Fundamento y objetivos: Se ha examinado la epidemiologia de las hepatitis A y E, que se transmiten por via gastroenterica, y de las hepatitis B y C, que se transmiten por via parenteral o sexual, en ninos de diferente condicion social residentes en la ciudad de Santa Cruz de la Sierra, Bolivia. Material y metodo: Se selecciono a 1.393 ninos de dos escuelas, una frecuentada por ninos que pertenecen a la mejor clase social de la ciudad (grupo A), y la otra, por ninos de clase social mas pobre (grupo B). Las muestras de sangre fueron obtenidas por medicos de la Universidad de Roma La Sapienza. Los anticuerpos sericos contra los virus de las hepatitis A, B, C y E, y el antigeno de superficie del virus B, se determinaron con metodos inmunoenzimaticos. La significacion se valoro con la prueba de la *2. Resultados: Los anticuerpos contra el virus A estaban presentes en el 82% de los ninos examinados, con una diferencia estadisticamente significativa entre ambos grupos (el 56,3 frente al 94,8%). La prevalencia de los anticuerpos anti-HBc y anti-HBs aumento con la edad, de modo que la infeccion se adquirio prevalentemente en la adolescencia, con una diferencia estadisticamente significativa entre los grupos A y B (el 1,1 frente al 3,8%). El mismo fenomeno se observo en la evaluacion de los anticuerpos anti-VHC (4,7% de positividad solo en el grupo B). Por ultimo, la presencia de anticuerpos contra el virus de la hepatitis E se observo solo en el 1,7% de la poblacion estudiada. Conclusiones: En Bolivia, como en otros paises en vias de desarrollo, las hepatitis viricas representan un grave problema de salud publica. La difusion de la hepatitis virica puede controlarse mejorando las condiciones higienicas y las costumbres de vida. Ademas, un plan de vacunacion contra los virus A y B de la hepatitis es indispensable para la poblacion que vive en un area endemica.

Prevalence of infections by hepatitis A, B, C and E viruses in two different socioeconomic groups of children from Santa Cruz, Bolivia

BACKGROUND AND OBJECTIVES The epidemiology of hepatitis A, E, B and C was analyzed in 1,393 children living in Santa Cruz de la Sierra, Bolivia. They were distributed in two groups according to the social condition. MATERIALS AND METHOD 1,393 children were selected from two different schools: one attended by children belonging to a high social class of the town (group A), and the other school attended by children belonging to the poorest social class (group B). Blood samples were drawn by a team of physicians from Rome University La Sapienza. Serum antibodies against hepatitis A, B, C and E virus, and the hepatitis B surface antigen were evaluated by immunometric methods. The significance was evaluated using the *2 test. RESULTS Antibodies against hepatitis A virus were detected in 82% of examined children, with a significant difference between the two groups (56.3% vs 94.8%). The incidence of anti-HBc antibodies increased with age, so the infection is acquired prevalently in adolescence with a significant difference between both groups (1.1% vs 3.8%). The same phenomenon was observed with anti-HCV antibodies (4.7% positivity only in group B). Serum antibodies against hepatitis E virus were observed in 1.7% cases. CONCLUSIONS In Bolivia, as in other developing countries, viral hepatitis represents a serious burden for public health. Spreading of viral hepatitis can be controlled upon improving hygienic conditions and customs. Moreover, a vaccination plan against hepatitis A and B virus is necessary for the population living in endemic areas.

Anti-neutrophil cytoplasmic antibodies in echinococcus granulosus hydatid disease.

The authors studied the presence of ANCA, evaluated by indirect immunofluorescence (IIF) and ELISA for anti-lactoferrin (LF), and anti-myeloperoxidase antibodies (anti-MPO), in sera of 69 patients with cystic echinococcosis (CE). According to Caremanis classification, 27 patients were considered to have active cysts and 42 patients were considered to have inactive cysts. ANCA were detected in 9 out of 27 patients (33.3%) with active cysts and in 3 out of 42 patients (7.1%) with inactive cysts. Differences between the two groups were statistically significant (P < 0.05). Anti-LF antibodies were found in seven patients (10.14%) and anti-MPO antibodies in ten patients (14.5%).

Development of factor VIII:C inhibitors following vaccination.

G.M. Ferri, MD, Department of’Medicina Clinica’, V.le dell’Università 37, I-00185 Rome (Italy) Acquired inhibitors against factor VIIL·C (FVIIL·C) in nonhemophilic patients are associated with various conditions, including autoimmune diseases (mainly rheumatoid arthritis and systemic lupus erythematosus), malignancies, the postpartum state, drug reactions, and dermatological disorders [1-4]. One case of circulating inhibitor associated with viral infection has also been described [5]. In this report, we describe the case of a 57-year-old male, diagnosed with lichenoid dermatosis, who developed severe hemorrhagic manifestations due to the appearance of inhibitors against FVIIL·C following vaccination with BCG and a pool of various strains of live attenuated corynebacteria. A 57-year-old male was admitted to our hospital in August 1989 with severe fatigue, bleeding from the gums, macroscopic hematuria, and spontaneous leg and forearm pain. He had no family or past history of a tendency to bleed. In September 1988, a lichenoid dermatosis of the scalp was diagnosed. Because of worsening of the skin lesions, vaccine therapy with BCG and a pool of various strains of live attenuated corynebacteria was advised, and was started in June 1989 in a private clinic, after the patient had given his informed consent. This therapeutic approach was adopted on the basis of preliminary unpublished results showing the efficacy of nonspecific immu-notherapy in lichenoid dermatosis. The vaccine was administered monthly by subcutaneous injection. Following the second booster, the hemorrhagic manifestations occurred. On examination, the patient appeared in poor general condition. Swelling of both calves and of the right forearm were present, due to the presence of hematomas. The liver and spleen were palpable 2 and 1 cm below the costal margin, respectively. Laboratory investigations revealed Hb 12.7 g/dl, WBC 5.2 × 109/1 (72% neutrophils, 26% lymphocytes, 1 % monocytes, and 1 % eosinophils), platelets 229 × 109/1 and ESR 80 mm in 1 h. Macroscopic hematuria was present. Liver enzymes, serum creatinine, and blood urea nitrogen were normal. Tests for VDRL, rheumatoid factors and antinuclear antibodies were negative. The prothrombin time (PT), the activated partial thromboplastin time (aPTT), and the quantification of ñbrinogen

Circulating anticoagulant against Factor XII and platelet antibodies in systemic lupus erythematosus.

A case of systemic lupus erythematosus is reported, with circulant anticoagulant against factor XII, associated with impaired platelet aggregation, presumably in relation to the presence of anti-plate