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W J Koopman

Publications and source records attributed to W J Koopman.

At least 73 records · Page 4Linked to original sources
PubMed1993

Severe axonal degeneration in acute Guillain-Barré syndrome: evidence of two different mechanisms?

Four cases of severe acute Guillain-Barré syndrome (GBS) characterized by severe axonal degeneration are presented. All had electrically inexcitable motor nerves as early as 4 days after onset. The disease was rapid in onset and the residual disability was severe. Two different types of pathology were seen. Nerve biopsies in 3 cases showed severe axonal degeneration without inflammation or demyelination. Autopsy in one of these cases showed that the dorsal and ventral roots were also significantly affected. These cases illustrate the primary axonal form of GBS. Nerve biopsy in the fourth case at day 15 showed marked inflammation and demyelination with axonal degeneration. Contralateral nerve biopsy at day 75 showed almost complete loss of axons. This case illustrates another type of axonal degeneration, that which occurs secondary to inflammation and demyelination.

Aged↗
PubMed1993

New approaches to the therapy of autoimmune diseases: rheumatoid arthritis as a paradigm.

Several therapeutic agents currently are used to treat rheumatoid arthritis (RA). However, there is no compelling evidence that any of these agents substantially alters the long-term destructive course of RA. Advances in biotechnology have led to a better understanding of mechanisms that underlie autoimmune diseases such as RA. Although the etiology of RA remains unknown, there now is considerable insight regarding the immune and inflammatory pathways that ultimately lead to cartilage and bone destruction. Therapies with monoclonal antibodies directed against cell surface constituents, fusion toxins against cell activation markers, and cytokine inhibitors all have been shown to be safe and possibly efficacious in early open trials in RA. They now are being more rigorously tested in double-blind, placebo-controlled trials. Early experience with these biologic agents in humans, as well as data obtained from the use of these agents in animal models of autoimmune disease, are reviewed. In addition, experimental studies with "blocking peptides" and immunization with autoreactive T cell receptor peptides will be reviewed, and implications for therapy in RA will be discussed.

Antibodies, Monoclonal↗
PubMed1993

Increased spontaneous secretion of rheumatoid factor by intestinal lamina propria mononuclear cells from Crohn's disease but not ulcerative colitis patients.

Increased levels of rheumatoid factors (RF) have been observed in the serum of Crohn's disease but not ulcerative colitis patients, and have been proposed to relate to an increased state of intestinal lymphocyte activation. We have therefore examined the spontaneous in vitro secretion of RF by intestinal lamina propria mononuclear cells (MNC) isolated from specimens from control and inflammatory bowel disease (Crohn's disease, ulcerative colitis) patients. Normal intestinal lamina propria MNC spontaneously secrete rheumatoid factors of different isotypes during 14 days of in vitro culture (9.7 ng/ml IgA RF, 11.6 ng/ml IgM RF and 64.6 ng/ml IgA anti-Fc (IgG)). In matched studies intestinal MNC isolated from normal large bowel exhibited significantly greater levels of RF synthesis and secretion in vitro than normal small bowel intestinal MNC. A large increase in spontaneous RF secretion was observed from Crohn's disease intestinal MNC (21.4 ng/ml IgA RF, 21.4 ng/ml IgM RF, and 108.15 ng/ml IgA anti-Fc (IgG)), when compared with normal controls. The amount of RF secreted was dependent on the amount of inflammatory activity of the bowel specimens, from which the MNC were isolated (198.3 ng/ml of IgA anti-Fc(IgG) from involved versus 50.0 ng/ml from matched non-involved tissue). Ulcerative colitis MNC released decreased amounts of RF (7.1 ng/ml IgA RF, 6.2 ng/ml IgM RF, and 42.3 ng/ml IgA anti-Fc(IgG)). These observations using isolated intestinal MNC may explain the findings of RF changes in the sera of inflammatory bowel disease patients. Our observations support the hypothesis of a heightened state of activation in normal intestinal lamina propria MNC, which is further increased in active Crohn's disease. The dissimilarities observed between Crohn's disease and ulcerative colitis may indicate fundamental differences in disease pathophysiology and will lead to further studies exploring intestinal immunoregulatory properties of RF.

Antibodies, Anti-Idiotypic↗
PubMed1993

Anticardiolipin antibodies in systemic lupus erythematosus: clinical correlates, HLA associations, and impact on survival.

OBJECTIVE: To determine the frequency and clinical and HLA associations of anticardiolipin (aCL) antibodies in patients with systemic lupus erythematosus (SLE), as well as their impact on survival. METHODS: We studied 139 patients with SLE seen at a university based practice. We tested for clinical, laboratory, and HLA associations with levels of aCL antibody isotypes either in sera available in the bank (distant past) or in 2 samples. Demographic, clinical, laboratory, and HLA data were subjected to univariate survival analysis; variables of importance were entered into Cox multivariate regression analyses. RESULTS: aCL antibodies (any isotype) were present in 57 (41.0%) of the 139 patients tested in the distant past sample, and in 23 (32.3%) as a persistent event in the 71 patient subgroup tested twice. IgG aCL were significantly associated with deep venous thrombosis (DVT) (p = 0.04). No other clinical or HLA association was found with aCL positivity. In the survival analyses, older age at diagnosis, presence of major infections, endstage renal disease, and IgM aCL antibody positivity in the distant past emerged as important independent factors adversely affecting survival. In the subgroup tested twice for aCL antibodies (n = 71), persistent IgM aCL antibody positivity (n = 10) emerged as an important independent factor. Among the subgroup of patients that had HLA data available (n = 88), HLA-DQw7 and thromboembolic events also adversely affected survival. CONCLUSION: We confirmed the association of IgG aCL antibody positivity with DVT, and the impact on survival of endstage renal disease, major infections, and older age at diagnosis. IgM aCL antibody positivity present either as an isolated event in the distant past or as a persistent finding, thromboembolic events, and HLA-DQw7 emerged as important prognostic factors.

Adult↗
PubMed1993

Do nonimmunologically mediated pathways play a role in the pathogenesis of rheumatoid arthritis?

The association between elevated serum rheumatoid factor and rheumatoid arthritis (RA) has been confirmed repeatedly and interpreted as strong evidence for an immunologic basis for the disease. In recent years, considerable additional evidence supporting this view has been obtained, strongly suggesting a role for CD4+ T cells in the pathogenesis of RA. An alternative view has also gained support, however. Based on studies of animal models and of RA itself, several lines of evidence have emerged that indicate that nonimmunologic pathways are operative in established RA. These observations have fostered the hypothesis that the evolution of RA may be associated with the emergence of non-T-cell-dependent autonomous pathways that dominate the latter stages of the disease.

Antibody Formation↗
PubMed1993

Analysis of immunoglobulin gamma heavy chain expression in synovial tissue of a patient with rheumatoid arthritis.

OBJECTIVE: To gain insight into mechanisms underlying local immune responses in rheumatoid arthritis (RA), we analyzed the utilization of variable-region heavy chain (VH), diversity (DH), and joining (JH) gene segments expressed in synovial tissue of a patient with RA. METHODS: An unrestricted complementary DNA (cDNA) library was generated from unselected cells extracted from synovial tissue obtained at the time of joint replacement. Southern blot analysis for VH, JH, and C gamma subclass utilization was performed on the first 50 C gamma- and JH-positive recombinants for which phage DNA was isolated. Eighteen of the clones were selected at random for sequence analysis. The VH gene segments were compared with an extensive database of germline and cDNA sequences. RESULTS: All transcripts utilized gene segments from the VH1 (28%), VH3 (56%), and VH4 (15%) families. There was a predominance of JH4, JH5, and JH6 gene segment utilization. Fourteen of 18 randomly sequenced clones contained sufficient VH-region information for analysis. Eight (57%) were most closely related to VH gene segments that are preferentially expressed in human fetal liver or that encode antibodies with self-reactivity. The variable domains were heavily mutated, and replacement-to-silent substitution ratios (R:S ratios) in the antigen-binding domains (complementarity-determining regions [CDRs]) were disproportionately high. CDR3 lengths were quite variable, due to extensive N-region addition and 5'-exonuclease activity in the VH-DH-JH joins. CONCLUSION: Plasma cells in this synovial tissue sample appear to express VH gene segments that are preferentially utilized during fetal development or in autoantibodies. The JH repertoire is similar to that seen in adult peripheral blood lymphocytes, but much different from that found during fetal development. The large number of somatic mutations and the high R:S ratios in the CDRs suggest an antigen-driven response.

Amino Acid Sequence↗
PubMed1993

Host factors in the pathogenesis of arthritis triggered by infectious organisms. Overview.

Individual variability in host immune responses to infectious agents is likely influenced by differences in the repertoires of antigenic peptides bound by self-major histocompatibility complex molecules (MHC) and in the repertoires of T-cell receptors expressed in each individual. Moreover, genes regulating the processing of foreign MHC antigens (for example, peptide pump genes and proteosome constituent genes) may also be important in this regard. Infectious organisms may subvert host immune responses through expression of constituents sharing structure homology with host molecules. Such structural mimicry may serve to either promote induction of potentially harmful cross-reactive autoimmune responses or impede effective host responses, thereby favoring persistence of the organism.

Arthritis, Infectious↗
PubMed1992

A rheumatoid factor from a normal individual encoded by VH2 and V kappa II gene segments.

OBJECTIVE: To gain insight into the immunoglobulin variable-region repertoire of anti-IgG antibodies (rheumatoid factors [RF]), we characterized the VH and V kappa gene segments utilized in an IgM-RF-secreting lymphoblastoid cell line (SSH23) isolated from a normal individual. METHODS: The cell line SSH23 was established by Epstein-Barr virus transformation of peripheral blood non-T mononuclear cells. First-strand complementary DNA (cDNA) was generated and used for polymerase chain reaction amplification of the heavy and light chain variable domains. The amplified variable domains were sequenced and compared with an extensive database of germline and cDNA V gene segments. RESULTS: The VH sequence was found to be identical to a previously described fetal VH2 incomplete cDNA and to differ by only 3 nucleotides from a JH proximal germline VH2 gene segment. To our knowledge, this is the first example of a VH2 rheumatoid factor. The V kappa 2-J kappa 4 light chain contains an uncommon 10-amino acid third complementarity-determining region (CDR 3). CONCLUSION: Utilization of preimmune fetal VH gene segments and unusual light chain junctional diversity appear to be features shared by many physiologic and pathologic rheumatoid factors.

Amino Acid Sequence↗
PubMed1992

The immunoglobulin kappa light chain repertoire expressed in the synovium of a patient with rheumatoid arthritis.

OBJECTIVE: To analyze the nature of the B cell response in the synovial tissue of a patient with rheumatoid arthritis (RA). Specifically, we sought to determine if the pattern of immunoglobulin expression was consistent with polyclonal stimulation of B cells or an antigen-driven response. METHODS: We generated an unrestricted complementary DNA (cDNA) library from the diseased synovium of a rheumatoid factor (RF)-positive patient with an 18-year history of RA. A random sample of kappa light chain recombinants was identified, and sequence analysis was performed. The variable domains were compared with an extensive database of germline and cDNA kappa sequences. RESULTS: We found a light chain repertoire enriched for kappa transcripts containing 2 V kappa gene segments (Humkv325 and Humkv328) that are frequently associated with paraproteins expressing RF activity. Kappa variable domains from synovium contained numerous somatic mutations which resulted in frequent replacement of amino acids that encode the classic antigen-binding site. Unexpectedly, many of these kappa transcripts contained non-germline-encoded nucleotides (N regions) at the site of V kappa-J kappa joining. The combination of N-region addition and variation in the sites of V kappa-J kappa splicing generated unusually long complementarity-determining region 3 regions and charged amino acids near the V kappa-J kappa splice site. CONCLUSION: The pattern of somatic mutations found in this patient sample supports the hypothesis that these synovium-derived plasma cells are the product of immunoglobulin receptor-dependent (i.e., antigen-driven) selection. The extent of N-region addition raised the additional possibility that these antibodies derive from an unusual set of B lymphocytes that have escaped normal regulation.

Amino Acid Sequence↗
PubMed1992

Efficacy and safety of 10-deazaaminopterin in the treatment of rheumatoid arthritis. A one-year continuation, double-blind study.

OBJECTIVE: To determine the long-term safety and efficacy of 10-deazaaminopterin (10-DAM) in the treatment of rheumatoid arthritis (RA). METHODS: A 1-year continuation of an initial 15-week randomized, double-blind clinical trial of 10-DAM and methotrexate (MTX). RESULTS: 10-DAM (n = 10) and MTX (n = 8) had comparable safety and efficacy profiles. One 10-DAM-treated and 2 MTX-treated patients experienced transient side effects; 1 MTX-treated patient experienced recurrent nausea and discontinued MTX. CONCLUSION: 10-DAM appears to be as beneficial and as safe as MTX for the treatment of RA.

Adult↗
PubMed1992

Scanning electron microscopic evaluation of the arthritis in MRL/lpr mice.

The articular surfaces of disarticulated knee joints from MRL/lpr and MRL/n mice, aged 4-33 weeks were examined by light microscopy (LM) and scanning electron microscopy (SEM). Light microscopy did not reliably predict SEM findings. Most of the abnormalities detected by SEM were related to surface disruption of articular cartilage. However, areas of articular cartilage covered by tightly adherent non-confluent monolayers of stellate-shaped cells with intertwining cytoplasmic processes were observed. In these areas the integrity of the underlying cartilage matrix was disrupted, with exposure of collagen fibers. These findings suggested that outgrowth of proliferating synovial cells in the joints of arthritic MRL/lpr mice may lead to cartilage destruction.

Animals↗
PubMed1992

Abnormal galactosylation of serum IgG in patients with systemic lupus erythematosus and members of families with high frequency of autoimmune diseases.

Gas chromatographic carbohydrate analyses of IgG from 30 patients with idiopathic systemic lupus erythematosus (SLE) revealed lower content of galactose when compared to that in 36 controls of similar ages (mean +/- SD, 3.18 +/- 0.66 vs 3.82 +/- 0.41 galactose residues/mole of IgG, P < 0.001). Abnormal galactosylation was observed in 60% of SLE patients. Analyses of IgG from 58 members of five families, characterized by a high frequency of SLE and other autoimmune diseases and serological abnormalities, and 51 controls of similar age range revealed that IgG galactose deficiency was detectable not only in some members with clinical and serological abnormalities (P < or = 0.001), but also in those without evidence of autoimmune diseases or abnormal serologies (P < or = 0.001). These data indicate that abnormal galactosylation of IgG frequently occurs in asymptomatic members of families with a high frequency of SLE and other autoimmune diseases and suggests that this abnormality may be an indicator for the development of these diseases.

Adult↗
PubMed1992

Long-term treatment of the MRL/lpr mouse with methotrexate and 10-deazaaminopterin.

Female MRL/lpr mice were treated with I.P. doses of methotrexate (MTX) and 10-deazaaminopterin (DAAM) in the range of 1 to 100 mg/kg body weight/week, in two equally divided doses. Treatment began at 7 weeks of age and continued to 30 weeks of age. Joint histopathology scores were tightly correlated with skin lesion-proteinuria scores at 30 weeks of age. MTX at levels of 5, 25, and 100 mg/kg body weight/week and DAAM at a level of 25 mg/kg body weight/week significantly reduced skin lesion-proteinuria scores below controls in a dose dependent manner. Animals receiving MTX at 25 mg/kg body weight/week had a significantly longer median life span and animals receiving MTX at 100 mg/kg body weight/week had a greater than 15% suppression of growth when compared with controls. Longevity and skin lesion-proteinuria scores appeared to be good indicators of drug efficacy while growth suppression appeared to be a good indicator of drug toxicity.

Aminopterin↗
PubMed1992

Recurrent Guillain-Barré syndrome. Clinical and laboratory features.

The clinical and laboratory features of recurrent Guillain-Barré syndrome (RGBS) were reviewed in 12 patients in whom a total of 32 episodes fulfilled accepted criteria for Guillain-Barré syndrome (GBS). All patients were asymptomatic or only mildly symptomatic between attacks. In a given patient, the time to reach peak deficit from the onset of symptoms, the functional grade at peak deficit and the duration of the intervals between episodes varied considerably and unpredictably from one episode to the next. Analysis of these parameters across the entire group revealed no significant change as the number of attacks increased. The distribution of weakness varied between episodes with the possible exception of features of the Miller Fisher variant which were more constant. Tremor was noted in two patients and enlarged nerves in one patient. There was no evident response to immunosuppressive therapy. Results of cerebrospinal fluid (CSF) analysis and nerve conduction studies during recurrences were those expected in typical monophasic GBS. On nerve biopsy, onion bulb formations were sometimes observed after several recurrences. The following characteristics of RGBS may be sufficiently distinctive from those of chronic relapsing polyneuropathy to justify their nosological separation: rapid onset of symptoms with subsequent complete or near complete recovery, high incidence of an antecedent illness, lack of an apparent response to immunosuppressive therapy and normal CSF protein levels at the onset of a recurrence.

Adolescent↗
PubMed1992

Controlled trial of methotrexate versus 10-deazaaminopterin in the treatment of rheumatoid arthritis.

A 15 week double blind controlled trial of methotrexate and 10-deazaaminopterin for the treatment of rheumatoid arthritis (RA) was performed in 26 patients. Significant improvement in all measured clinical parameters was observed in the two patient groups. The drugs were well tolerated; only one patient (10-deazaaminopterin) withdrew from the study because of side effects. It is concluded that, in the context of this relatively short clinical trial, 10-deazaaminopterin is at least as beneficial as methotrexate in the treatment of RA.

Aminopterin↗