Central nervous system involvement in systemic lupus erythematosus: cerebral imaging and serological profile in patients with and without overt neuropsychiatric manifestations.

The aim of this study was to evaluate morphological and functional abnormalities by cerebral imaging in a series of systemic lupus erythematosus (SLE) patients with and without overt central nervous system (CNS) manifestations, and to detect possible relationships with clinical parameters and a large panel of autoantibodies, including those reactive against neurotypic and gliotypic antigens. 68 patients with SLE were investigated in a cross-sectional study which included clinical evaluation of symptoms, cerebral magnetic resonance imaging (MRI) and brain single photon emission tomography (SPECT) analysis, electroencephalography (EEG), and serological tests for antibodies directed against nuclear, cytoplasmic neuronal and glial cell-related antigens. The results of this study showed: (1) a significant positive association of (a) anti-glial fibrillary acidic protein (GFAP) serum antibodies with neuropsychiatric (NP) manifestations and (b) anti-serin proteinase 3 (anti-PR3/c-ANCA) serum antibodies with pathological cerebral SPECT; (2) the presence of significantly higher values of (a) SLICC organ damage index in patients with abnormal MRI and (b) SLAM activity index in patients with abnormal SPECT; and (3) the association of (a) abnormal MRI with nonactive NP manifestations and (b) combined abnormality of brain SPECT and MRI with the occurrence of overall overt NP manifestations and with those of the organic/major type. Neuropsychiatric manifestations, namely those of the organic/major type, appeared to be significantly associated to the presence of a serum antibody against GFAP, a gliotypic antigen. There was also evidence of an association between SPECT abnormality and the presence of anti-PR3 (c-ANCA). Furthermore, brain imaging by MRI and SPECT applied to SLE patients appears to express CNS involvement significantly related to specific categories of NP manifestations. The abnormalities detected by the two tests seem to be preferentially associated with different activity phases of the NP disorder or of the lupus disease.

Detection of antibodies to gangliosides and glycolipids in various intravenous immunoglobulin (IVIg) preparations.

The aim of this study was to examine the presence of antibodies to GM1 and sulfatide in various IVIg preparations. Five brands of commercially available human IVIg (Sandoglobulin, Isiven, Cytogam, Omrigam and Cutter) were examined and compared. Serial dilutions of each of the above preparations were prepared at a working range of 0.009 to 25.0 mg/ml IVIg, and screened by a standard 96-well microplate EIA for autoantibodies to the ganglioside GM1 and to the glycolipid sulfatide. The various IVIg preparations (Omrigam, Cytogam, Sandoglobulin, Isiven), except for Cutter IVIg, contained low to medium titers of the autoantibodies tested. Omrigam and Cytogam IVIg contained low titer of antibodies to GM1, and medium-titer of antibodies to sulfatide, whereas Sandoglobulin and Isiven contained only low-titer of autoantibodies to sulfatide. The presence of natural autoantibodies to myelin in human sera may explain the presence of the tested antibodies within IVIg preparations. Measurements of antibodies to ganglioside and glycolipid in sera of Guillain-Barré patients immediately following IVIg, would probably not reveal antibody decrease. Alternatively, long-term (several weeks) follow-up of titers might result in their modification due to inhibition of antibodies production by IVIg.

A study of 20 SLE patients with intravenous immunoglobulin--clinical and serologic response.

OBJECTIVE: To test the clinical response of systemic lupus erythematosus (SLE) patients to intravenous immunoglobulins (IVIg), and whether the clinical response of IVIg treatment in SLE is accompanied by modification of SLE-associated autoantibodies/antibodies (Abs) and complement levels. METHODS: Twenty SLE patients were treated with high-dose (2 g/kg) IVIg monthly, in a 5-d schedule. Each patient received between 1-8 treatment courses. They were evaluated for the clinical response, Systemic Lupus Activity Measure (SLAM) score before and after IVIg, levels of antinuclear antibody (ANA), dsDNA (double-stranded DNA), SS-A or SS-B, ENA (extractable nuclear antigens), C3 and C4 levels before and after the treatment, and before and after each treatment course. RESULTS: A beneficial clinical response following IVIg treatment was noted in 17 out of 20 patients (85%). Few clinical manifestations responded more to treatment: arthritis, fever, thrombocytopenia, and neuropsychiatric lupus. In 9 patients evaluated before and after IVIg, mean SLAM score decreased from 19. 3+/-4.7 to 4+/-2.9 (P<0.0001). There was a tendency towards abnormal levels of complement and Abs before IVIg courses among the treatment responders compared with the non-responders, and similarly the former tended to have normalization of their abnormal levels more than the latter. These differences were found statistically significant only with respect to C4 and SS-A or SS-B levels before IVIg courses. CONCLUSION: IVIg has a high response rate among SLE patients. A combination of clinical manifestations, Abs and complement levels may aid in the future in predicting who among SLE patients will benefit more from IVIg treatment.

Serologic and clinical response to treatment of systemic vasculitis and associated autoimmune disease with intravenous immunoglobulin.

BACKGROUND: Autoimmune vasculitides cannot always be controlled by steroids and immunosuppressive drugs. Intravenous immunoglobulin (IVIg) treatment was found beneficial in several vasculitides including systemic and organ-specific diseases. In this article we tested whether the beneficial clinical response of IVIg treatment in vasculitides was accompanied by a decrease in vasculitis-associated autoantibody levels. METHODS: Ten patients diagnosed as having vasculitis were treated with high-dose (2 g/kg) IVIg monthly, in a 5-day schedule. In all the patients, other therapeutic measures failed to control disease progression prior to IVIg treatment. Each patient received between 1 and 6 treatment courses. All patients were evaluated for the levels of 5 autoantibodies (Abs) related to vasculitis before and after each treatment course. RESULTS: In 6 out of the 10 patients, a beneficial clinical response followed IVIg treatment. Moreover, no treatment-related adverse effects were observed in any of the patients. Anti-myeloperoxidase antibodies and cytoplasmic-antineutrophil cytoplasmic antibodies levels decreased concomitantly with the clinical improvement observed in the patients with Churg-Strauss vasculitis and Wegener's granulomatosis, respectively. Levels of cytoplasmic-antineutrophil cytoplasmic antibodies (ANCA) with specificity for bacteridial/permeability-increasing protein and human lysosomal-associated membrane protein increased after each treatment course, but returned to normal values before the following one. CONCLUSIONS: When other therapeutic measures, such as immunosuppressive therapy, fails to control disease manifestations in patients with vasculitides, IVIg is a possible effective intervention method with a high response rate. IVIg probably exerted its effects on disease progression via different mechanisms. Among these mechanisms, a decrease in relevant Ab levels is often found (probably by anti-idiotypes in IVIg), and thus ANCA levels are expected to associate with disease activity.

Autoantibodies in neurodegenerative diseases: antigen-specific frequencies and intrathecal analysis.

The frequency of autoantibodies (AAbs) was surveyed in several neurodegenerative diseases, other neurological diseases, and controls using antigen-specific EIAs for neurofilament heavy subunit, tubulin, glial fibrillary acidic protein, S100 protein, tau, beta-amyloid peptide, myelin basic protein, and heparan sulfate proteoglycan. High frequencies of sera and cerebrospinal fluid tubulin AAbs were found in Alzheimer disease (62% and 69%, respectively), Parkinson disease (27% and 70%), amyotrophic lateral sclerosis (54% and 67%), and in sera from multiple sclerosis (50% and 67%), optic neuritis (85%), Guillain-Barré syndrome (88%), and vascular dementia (52%). High frequencies of neurofilament heavy subunit AAbs were detected in Guillain-Barré syndrome, chronic peripheral neuropathy (88%) and optic neuritis (62%); whereas, some Alzheimer's disease (33%) and vascular dementia (44%) patients had glial fibrillary acidic protein AAbs. Lower frequencies of other AAbs were found in patient groups. AAb results were also compared to functional assessment of blood-brain barrier integrity in Parkinson's disease and Alzheimer's disease. The relevance of these AAbs to pathogenesis and/or course of neurologic diseases merits further study with particular reference to subgrouping and prognosis.

Autoantibody level modification in adult patients with idiopathic thrombocytopenic purpura following intravenous immunoglobulin treatment.

The aim of this study was to determine whether treatment of patients with immune thrombocytopenic purpura (ITP) with intravenous immunoglobulin (IVIg) is associated with a modification in the antiplatelet glycoprotein (GP) antibodies (Abs). Fourteen patients with ITP (11 females and 3 males, mean age 36.6 years, range 18-72) received one to four IVIg treatment courses. The preparation used was ISIVEN that was given in a dose of 2 g/kg body weight in a 5-day schedule and in monthly intervals. Levels of IgG, IgM and IgA isotypes of Abs to GPs IIb/IIIa and Ib/IX were measured before the treatment, and before and after each treatment course. Two patients did not respond to IVIg, 6 had a temporary response, 5 had a sustained response and 1 patient responded well to the treatment but was lost to follow-up. The patients had a high prevalence of serum Abs directed against GPs IIb/IIIa and Ib/IX before the treatment, and the mean IgG isotype levels of both Abs increased after each treatment course, and decreased again before the following course began. Whenever high Ab levels of either isotype (> 10 U/ml) were detected before the treatment, they were significantly decreased before the last treatment course. The elevated levels of IgG Abs to IIb/IIIa and Ib/IX after every course are probably a result of displacement of these Abs from Fc receptors by the IVIg, rather than of exogenous infusion of these Abs contained within the IVIg, whereas the decrease in high Ab levels after a few treatment courses results from the immunomodulatory effects of IVIg: suppression of Ab formation, and the presence of anti-idiotypes.

Autoantibody profile in the sera of women with hyperprolactinemia.

Prolactin (PRL) has been implicated as an important in vivo modulator of cellular and humoral immunity. In order to elucidate the impact of elevated serum PRL levels on the immune system, we measured circulating autoantibodies in the serum of 33 hyperprolactinemic (HPRL) women and in 19 healthy women with normal PRL levels. All sera were examined for the presence of autoantibodies against 15 different antigens, including: ssDNA, dsDNA, histones (H2AH2B), Sm, RNP, SS-A/Ro, SS-B/La, cardiolipin, Scl-70, Jo1, collagen, glomerular basement membrane (GBM), pyruvate dehydrogenase (PDH), proteinase-3 (PR3) and MPO. Twenty-five of 33 (75.7%) HPRL women were found to have at least one autoantibody, while none of the 19 women with normal PRL had any. Eight HPRL women had seven or more (up to nine) different autoantibodies. Some of the autoantibodies were more frequently expressed than others, namely: anti-ss-DNA, anti-dsDNA, anti-Sm, anti-PDH and anti-SS-A/Ro. Autoantibodies to the autoantigens tested are common in a variety of autoimmune and rheumatic disorders including systemic lupus erythematosus (SLE), Sjögren's syndrome, mixed connective tissue disease (MCTD), scleroderma, primary biliary cirrhosis (PBC), polymyositis/dermatomyositis and vasculitis. Yet none of the HPRL women whose serum was found to contain high titers of autoantibodies presented with symptoms related to the respective autoimmune disorders. Our results support the role of PRL in the regulation of immune responses in man.

Myelin- and microbe-specific antibodies in Guillain-Barré syndrome.

We surveyed the frequency of reported infections and target autoantigens in 56 Guillain Barré syndrome (GBS) patients by detecting antibodies to myelin and microbes. Sulfatide (43%), cardiolipin (48%), GD1a (15%), SGPG (11%), and GM3 (11%) antibodies were the most frequently detected heterogenous autoantibodies. A wide spectrum of antimicrobial IgG and IgM antibodies were also detected; mumps-specific IgG (66%), adenovirus-specific IgG (52%), varicella-zoster virus-specific IgG (46%), and S. pneumoniae serotype 7-specific IgG (45%) were the most prevalent. Our results indicate that polyclonal expansion of physiologic and pathologic antibodies and/or molecular mimicry likely occurs following infection and is related to other autoimmune factors in the etiology of GBS. Although no single definitive myelin-specific autoantibody was identified, our results suggest a unique pattern of reactivity against autoantigens.