Remission of demyelinating polyneuropathy with immunoadsorption, low dose corticosteroids and anti-CD20 monoclonal antibody.

Demyelinating polyneuropathy with anti-myelin associated glycoprotein (anti-MAG) antibodies is an immune mediated disorder characterized by proximal and distal symmetric weakness. Electrophysiological measurements depict features characteristic for demyelination, including prolonged distal latency, retarded conduction velocity, delayed or absent F-waves, and, rarely, partial conduction block. We report on a 65-year-old patient who was diagnosed with demyelinating polyneuropathy and anti-MAG antibodies five years before admission. Despite immunosuppressive agents and extracorporeal therapy (plasmapheresis) the disease progressed as assessed by clinical symptoms and neurological tests. Laboratory results showed an increase of serum immunoglobulin M and anti-MAG antibodies over time. Because of progressive disease we decided to treat the patient with immunoadsorption followed by application of the anti-CD20 antibody, rituximab. Six cycles of selective immunoadsorption were performed over three-weekly intervals with a repetitively used column (Globaffin); each cycle consisted of four consecutive daily treatments. Starting at cycle 4 the anti-CD20 antibody rituximab was administered with 375 mg/m(2) after immunoadsorption. The pretreatment anti-MAG antibody level of 10,000 U/mL, indicating disease activity, initially increased during treatment to a maximum of 30,559 U/mL. However, after completion of the six cycles, the anti-MAG level had decreased to 2348 U/mL; 16 months after the last immunoadsorption cycle the anti-MAG level had increased to 4134 U/mL, while the conduction velocity and compound motor action potentials remained stabile. Immunoadsorption in combination with a monoclonal anti-CD20 antibody in patients with demyelinating polyneuropathy with anti-MAG is effective and can be used an alternative treatment option in patients with progressive disease.

Early detection of Richter's transformation: stable disease with dose-reduced gemcitabine and local radiation.

BACKGROUND: The occurrence of Hodgkin's lymphoma (HL) as a second aggressive lymphoid malignancy (known as Hodgkin's disease variant of Richter's transformation) is rarely observed. Response rates, even with highly aggressive therapy such as stem cell transplantation, are limited, ranging from 4 to 43%, and the medium survival time ranges from 5 to 8 months. CASE REPORT: A 72-year-old patient with a history of chronic lymphatic leukemia (CLL) was admitted with thoracic back pain and assumed progression of the CLL. The patient showed no fever, night sweats or weight loss. A computed tomography (CT) scan confirmed the progression of axillary and cervical lymph nodes. In addition, an intraspinal infiltration at the 8th thoracic vertebra (Th8) was detected. Surprisingly, histology of an extirpated lymph node demonstrated the existence of 2 tumors in the same lymph node. Infiltrates of small lymphocytes representing the pre-existing CLL (CD5-, CD20-, CD23-positive) coexisted with Reed-Sternberg Hodgkin's cells (CD30-, CD15-positive). Chemotherapy was started, combined with palliative radiation of vertebrae Th7-Th10. 12 months after diagnosis of Richter's transformation the patient is still alive without any progression of the underlying disease. CONCLUSION: We present a unique case of a Hodgkin's disease variant of Richter's transformation and CLL in the same lymph node, which was detected early because of spinal infiltration and was subsequently stabilized with reduced-dosage gemcitabine and local radiation. Additionally, we show unique pictures of 2 tumors coexisting in the same lymph node.

Humoral immune response to citrullinated collagen type II determinants in early rheumatoid arthritis.

Collagen type II (CII) is a relevant joint-specific autoantigen in the pathogenesis of rheumatoid arthritis (RA). Whereas the reasons for the breakage of self tolerance to this major cartilage component are still enigmatic, T cell responses to glycosylated CII determinants in RA patients indicate that post-translational modifications play a role. Since the conversion of arginine into citrulline by peptidylarginine deiminases (PAD) in some non-joint-specific antigens such as filaggrin or fibrin has been shown to give rise to RA-specific humoral immune responses, we investigated whether PAD modification of cartilage-specific CII might affect its recognition by circulating autoantibodies in early RA. In vitro treatment with purified PAD led to arginine deimination of native CII or of synthetic CII peptides as evidenced by amino acid analysis. The citrullination resulted in modified recognition of the immunodominant CII epitope C1(III) (amino acid residues 359-369) by murine and human antibodies. In a cohort of early RA patients (n=286), IgG antibodies directed toward a synthetic citrullinated C1(III) peptide (citC1(III)-P) were detectable with a prevalence of 40.4%. The partial autoantibody cross-reactivity between citC1(III)-P and citrullinated peptides mimicking epitopes of the cytoskeletal autoantigen filaggrin suggests that autoimmunity to cartilage-specific modified self might be a critical intermediate bridging recognition of PAD-modified extra-articular autoantigens with the disruption of tolerance to native cartilage constituents.