Role of the mononuclear cell infiltrate in Graves' orbitopathy (GO): results of a large cohort study.

OBJECTIVE: The extent to which mononuclear cells and TSH-receptor autoantibodies (TRAb) contribute to Graves' orbitopathy (GO) is not completely defined. Here we investigated the relationship between the immunohistochemical phenotype of orbital infiltrating cells and GO features in a large number of patients. METHODS: We conducted an observational cohort study in 76 consecutive patients with GO (16 men and 60 women) who underwent orbital decompression over a period of 18 consecutive months. An ophthalmological evaluation was performed in all patients, as well as immunohistochemistry for CD3, CD4, CD8, CD56 (T-cell markers), CD25 (T and B-cell marker), CD20, CD19 (B-cell markers), and CD138 (plasmacell marker) in specimens collected at decompressive surgery. RESULTS: Having established cutoff values for each marker, cell infiltrates were found in 60 patients (78.9%; CD3: 39.4%, CD4 55.2%, CD8 50%, CD56: 0%, CD25: 28.9%, CD20: 51.3%, CD19: 25%, CD138: 26.3%). Eleven (14.4%) stained exclusively for CD138 (plasmacells). Patients with CD4-positive mononuclear cells had a significantly greater GO clinical activity score (CAS) (mean difference 1.07, 95% CI - 0.33 to - 1.82, P = 0.004 by univariate, P = 0.05 by multivariate analysis). CAS as well as the remaining GO features were not affected significantly by the mononuclear cell subpopulations in multivariate analyses. CONCLUSIONS: Mononuclear cell infiltrates are present in the majority of GO patients, with a small percentage represented exclusively by plasmacells. CD4 cells exert a major role on GO activity. These findings may represent a further advancement in the comprehension of GO pathogenesis.

Altered populations of natural killer cell and natural killer T cell subclasses in myasthenia gravis.

Since the innate immune system can influence the disease activity of myasthenia gravis (MG), such as during infection, the frequencies of natural killer (NK) cells and NKT cells were analyzed in the blood and thymus. Before therapy (thymectomy plus glucocorticoid), the MG patients with thymic hyperplasia, but not those with thymoma, showed increased frequencies of mature NKT cells (CD3(+)TCRV(alpha)24(+)CD161(bright)) in the blood, while the frequency of immature NKT cells was unaltered. In the blood of the patients with thymoma, but not those with hyperplasia, the frequency of cytotoxic subclass of NK cells (CD3(-)CD16(+)CD56(dim)) was lower than that of the control. These alterations returned to normal after therapy. The thymic frequencies of NKT cells and NK cells in MG thymuses were unaltered. These results suggest the involvement of both innate and acquired immunity in the disease activity of MG.

Subtyping of osteoarthritic synoviopathy.

OBJECTIVE: Osteoarthritis research is traditionally concentrating on events within the degenerated articular cartilage. Changes in the synovial membrane are largely neglected. In fact, they are generally interpreted as secondary to the cartilage changes and not pathogenetically involved in the disease process. In this study, we present a systematic analysis of the synovial reaction pattern in early and late stages of the osteoarthritic disease process. METHODS: A large series of synovial specimens derived from early and late stage osteoarthritic cartilage disease were investigated by histological and immunohistochemical means for tissue architecture and inflammatory cell infiltrates. For comparison, also samples with rheumatoid arthritis, seronegative arthritis, and septic arthritis were included as well as normal synovial membrane specimens. RESULTS: In all specimens derived from patients with diagnosed osteoarthritis alterations of the synovial tissue were observed. A large spectrum of alterations was found in different stages of osteoarthritic joint disease and four different basic pattern of synovial reactions could be identified: (i) hyperplastic, (ii) inflammatory, (iii) fibrotic, and (iv) detritus-rich synoviopathy. CONCLUSION: We show that in all cases of clinically overt osteoarthritic joint disease significant synovial pathology is associated. Furthermore, our study clearly documents that in osteoarthritic synovium significant inflammation can occur. This is suggestive of a distinct pathogenetic role of the synovium also in osteoarthritic cartilage degeneration at least in a subset of cases.

Human leucocyte differentiation antigens: review of the CD nomenclature.

In February 1989 the 4th International Workshop and Conference on Human Leucocyte Differentiation Antigens was held in Vienna. At this meeting the structure and function of recognized cellular antigens was reviewed and new antigens defined. In addition, information was obtained on the molecular genetics of antigens from gene cloning and sequencing. The CD (clusters of differentiation) nomenclature was extended, giving a total of 78 CD clusters, and some previously described CD groups revised and sub-divided. In this paper new information on the structure and function of leucocyte antigens presented at the meeting will be discussed. In addition, descriptions of the newly defined CD clusters and changes to established clusters will be outlined.

Selective loss of the CD4+ inducers of suppressor T cell subsets (2H4+) in active systemic lupus erythematosus.

We investigated 2H4+ and 4B4+ T cell subsets from the purified CD4+ helper/inducer and CD8+ suppressor/cytotoxic T cells in circulating blood of 15 patients with severe active systemic lupus erythematosus (SLE), 6 patients with inactive SLE, 5 patients with rheumatoid arthritis and seven healthy controls. The percentage of the total CD4+ T cells increased and CD8+ T cells decreased in all patients with active SLE. Of interest, however, all the patients with active SLE and central nervous system (CNS) disease had a selective decrease in the percentage of CD4+ 2H4+ T cell subsets in circulating blood that is responsible for induction of the CD8+ suppressor T cells. This loss of the CD4+ 2H4+ T cells was accompanied by an increase in the CD4+ 4B4+ T cell subsets, that are the true helper/inducers providing help for B cell immunoglobulin production. A marked decrease in the CD4+ 2H4+ cell subsets in the circulating blood of all patients with severe active SLE and CNS disease is related with meaningful functional properties of the T cells in an abnormal immune system.

Comparative analysis of CD4-4B4 and CD4-2H4 lymphocyte subpopulations in HIV negative homosexual, HIV seropositive and healthy subjects.

A comparative analysis of subsets (4B4 and 2H4) within the CD4 lymphocyte subpopulation was made by double marker analysis among 23 healthy heterosexual, 16 healthy HIV seronegative high-risk homosexuals and 82 HIV seropositive subjects. Data show that the significant increase in CD4 lymphocytes observed among seronegative homosexuals corresponds mainly to an increase in CD4-4B4 positive cells while CD4-2H4 subset levels remain comparable to healthy heterosexual controls. A decrease both in CD4-4B4 and CD4-2H4, parallel to a decrease in CD4 subpopulation, was observed in asymptomatic seropositive carriers (SPC) and patients with ARC syndrome (AIDS-related complex) or AIDS (acquired immunodeficiency syndrome). Interestingly, an absolute decrease in CD4 subpopulation in patients with asymptomatic lymph node enlargement (LAS), is chiefly accounted for by a decrease in CD4-4B4 subset. The values of CD4-2H4 subset are significantly higher than those observed for SPC patients and are close to the normal values. These observations are of interest, as no differences between SPC and LAS patients could be detected when CD3, CD4 and CD8 subpopulations were studied.