A. Lamour

Conjunctival epithelial cells from patients with Sjögren's syndrome inappropriately express major histocompatibility complex molecules, La(SSB) antigen, and heat-shock proteins

The La(SSB) antigen has been detected within the cytoplasm and on the membrane of conjunctival cells (CC) from patients with Sjögrens syndrome, whereas it was weakly expressed in the nucleus of normal cells. The diseased CC were shown to overproduce major histocompatibility complex (MHC) class I antigens and express MHC class II antigens. Anti-heat-shock protein monoclonal antibody bound to the cell membrane in patients but not in normal controls.

Anti-Golgi Complex Autoantibodies in Patients with Primary Sjogren's Syndrome

Commencing with the monograph by Henrik Sjogren (1), a number of investigators have delineated the numerous aspects of sicca syndrome (2-5), since then referred to as Sjogrens syndrome (SS). This disorder is characterized by an infiltration of lymphocytes and plasma cells into the exocrine glands, with resultant xerostomia and keratoconjunctivitis sicca. It can occur alone (primary SS), or in conjunction with another autoimmune disease, such as rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE).Production of a variety of autoantibodies is one of the immunological hallmarks of the syndrome (6). Of particular interest is the anti-Golgi complex (AGC) antibody, first detected by Rodriguez et al. (7) in 1982. This description was refined and extended by Fritzler et al. (8), but surprisingly very little information is available about this autoantibody.

Galactose terminating oligosaccharides of IgG in patients with primary Sjögren's syndrome

Using a simple but novel ELISA, we have screened 40 serum samples from patients with primary Sjögrens syndrome and 34 normal controls for IgG glycosylation deficiencies, identified by their specific ricin binding. Elevated levels of asialylated IgG were detected in 24 patients. The extent of asialylation was significantly higher in the patients with extraglandular manifestations than in the others. Interestingly, the correlation of asialylated IgG was apparent only with Raynauds phenomenon and arthritis, and not other extraglandular manifestations. Strong correlations (P less than 0.01) were noted between asialylated IgG and rheumatoid factor or IgA-containing immune complexes.

CD5+ B cells and the immune system

The CD5+ B-cell population is prominent in early life and may play a key role in the ontogeny of the immune system. Transplantation studies in mice are in support of CD5+ B cells as a separate lineage from CD5- B cells. In both mice and men there is evidence in favour of CD5 being an activation antigen rather than a lineage marker, but the jury is still out! The frequency of CD5+ B cells appears to be under genetic influence. CD5+ B cells are receptive to many cytokines including IL-2 and IL-5 and themselves produce a number of cytokines especially IL-10. The function of the CD5 molecule on B cells is presently unknown but it might be involved in interaction with CD72 on other B cells. CD5+ B cells generally utilise minimally mutated germ-line genes and produce low avidity auto- and polyreactive antibodies (natural antibodies) generally of the IgM class.

Relationship of interleukin-4 to isotypic distribution of anti-double-stranded DNA antibodies in systemic lupus erythematosus.

IgG subclasses of anti-double-stranded DNA antibodies were determined in 182 patients with systemic lupus erythematosus. All isotypes were detected, but IgG1 and IgG3 were predominant (62 and 51% of the cases, respectively). An average of 64 +/- 27% was IgG1, 16 +/- 22% IgG2, 16 +/- 19% IgG3 and 4 +/- 10% IgG4. The rank order or frequency was IgG1, IgG3, IgG2 and IgG4 in patients with musculoskeletal involvement; IgG1, IgG2, IgG3 and IgG4 in those with renal complications; IgG3, IgG1, IgG2 and IgG4 in those with cutaneous involvement; and IgG1, IgG3, IgG2 and IgG4 in those with hematological manifestations. Interleukin-4 (IL-4) was detectable in 17 of 36 selected patients, as opposed to 1 of 40 normal controls. The percentage of the total autoantibody contributed by IgG1 was significantly higher (p < 0.03) in these patients than in the remainder with undetectable levels of IL-4.

Expression of CD5 and CD72 on T and B cell subsets in rheumatoid arthritis and Sjögren's syndrome.

A minority of B cells express the CDS marker, which is found on virtually all T cells, and CD72 has been defined as the CD5 ligand on the B cell membrane. The mean fluorescence intensity (MFI)of the CD5 molecules was shown to be higher on CD4+ CD29+ than CD4+ CD45RA+ in peripheral blood (PB) and synovial fluid (SF) of rheumatoid arthritis (RA) patients (P < 0.0001 and < 0.001), and PB of Sjogrens syndrome (SS) patients and normal controls (P < 0.02 and < 0.03). This MFI declined once the CD4 expressed HLA‐DR in PB of SS patients (P 0.004) and normal controls (P 0.02) or CD25 in PB of RA (P < 0.004) and SS patients (P < 0.0004). There was a correlation between the CDS MFI on CD4+ CD45RA+ and CD4+ CD29+ in RA (P 0.001) as well as SS (P 0.0007) PB. The CD72 MFI was impressively higher on CD5+ than CD5 B cells in PB and SF of RA patients (P < 0.0001 and P < 0.005) and PB of SS patients (P < 0.005) and normal controls (P < 0.005). Our data suggest that, in association with CD4CD29, CD5 is involved in CD5+B/CD5+ B cell interactions in non‐organ‐specific autoimmune diseases.

Cell-free Fc-gamma receptor III in sera from patients with systemic lupus erythematosus: correlation with clinical and biological features.

Fifty patients (41 females and 9 males, ranging in age from 12 to 79 years) with systemic lupus erythematosus (SLE) and 20 normal controls were evaluated for the presence of plasma cell-free Fc gamma receptor III (Fc gamma RIII) using an ELISA based upon a sandwich of two monoclonal antibodies. The standard curve was obtained with serial dilutions of recombinant Fc gamma RIII. In the patients, the cell-free Fc gamma RIII levels ranged from to 1.76 micrograms/ml, while it did not exceed 0.21 microgram/ml in the controls. Assuming that the cutoff is 0.25 microgram/ml, 11 SLE patients and no controls had elevated cell-free Fc gamma RIII levels in the serum. Among the SLE patients, the level of cell-free Fc gamma RIII was significantly lower (p = 0.05) in 4 patients with sicca syndrome than in the remaining 46. Furthermore, cell-free Fc gamma RIII levels appeared to be lower in 11 patients with renal involvement than in those without. For the biological parameters, we observed that the 27 patients who presented lymphopenia also had a lower level of cell-free Fc gamma RIII when compared to the 23 patients without lymphopenia (0.09 +/- 0.19 versus 0.35 +/- 0.52 microgram/ml; p = 0.05). Circulating cell-free Fc gamma RIII may originate from shedding by presumably activated polymorphonuclear cells.

Activation of peripheral blood lymphocytes in patients with primary sjögren's syndrome

SummaryThe peripheral blood from 15 patients with primary Sjögrens syndrome and from 15 matched controls was examined for the presence of activated T and B lymphocytes, by using monoclonal antibodies directed to interleukin-2 (IL-2) and transferrin receptors, and to HLA-DR determinants. The number of circulating positive-T cells was significantly greater in the patients than in the controls, irrespective of disease activity. There were more of the CD8 cells than of the CD4 cells that expressed IL-2 receptors. There was a small but significant increase in activated B cells in the patients, since this population is virtually absent from the normal blood.

The majority of FcγRIII-positive γδT cells do not express HLA-DR in patients with primary Sjögren's syndrome

Abstract The percentages of circulating γδT cells and the proportions of these expressing FcγRIII (CD16) or HLA-DR in patients with primary Sjogrens syndrome (pSS) and controls were determined using monoclonal antibodies and flow cytometry. There was no significant difference in the percentages of γδT cells in the pSS patients compared with controls. There was, however, a significant increase in the proportions of both CD16 + and HLA-DR + γδT cells in pSS patients. A 3-colour immunofluorescence technique demonstrated that these two markers were mutually exclusive and therefore may identify either subpopulations of γδT cells or different stages of the activation process.

Prognostic significance of cytotoxic T cells in individuals infected with human immunodeficiency virus

Nine dual-fluorescence combinations were used to enumerate T-cell subsets in 112 human immunodeficiency virus type 1-infected patients. Two blood samples were analyzed, with a 6-month interval between the tests, in 53 of these 112 patients. The alteration in CD4 over this period of time correlated with the change in CD8 and CD8S6F1 (P<0.02 andP<0.01), irrespective of the disease stage. Two groups of patients were defined by the CD8S6F1 subset at the first normal levels. Changes in numbers of CD4, CD4CD45RA, and CD4CD29 were significantly higher in group B than in group A patients. The absolute count of CD8S6F1 could thus serve as an indicator of the ensuing depletion of the CD4 population, as well as the CD4 subsets.