Monoclonal IgMs with anti-Gal(beta 1-3) GalNAc activity in lower motor neuron disease; identification of glycoprotein antigens in neural tissue and cross-reactivity with serum immunoglobulins

IgM monoclonal antibodies (M-proteins) with anti-Gal(beta 1-3)GalNAc and anti-Gal(beta 1-3)GlcNAc activity that bind to gangliosides GD1b and GM1, from two patients with lower motor neuron disease were tested for binding to neural glycoproteins. The M-proteins bound to several glycoproteins in the central and peripheral nervous system including to some in the non-myelin or axonal fraction only. Peanut agglutinin (PNA) which is specific for Gal(beta 1-3)GalNAc, bound to the same protein bands. Since serological studies revealed that the M-proteins were complexed to IgG, serum immunoglobulins were tested for presence of Gal(beta 1-3)GalNAc epitopes. Both PNA and the M-proteins bound to immunoglobulin heavy and light chains, suggesting that the circulating M-proteins bind to Gal(beta 1-3)GalNAc on other immunoglobulins. These studies indicate that in addition to gangliosides the M-proteins might bind to Gal(beta 1-3)GalNAc bearing glycoproteins in vivo and that carbohydrate epitopes on immunoglobulins might have a role in the development and regulation of autoantibodies which cross-react with neural antigens and may cause neurological disease.     

Extension and flexion torque variability in ACL deficiency

Purpose  

To evaluate possible differences in knee extension and flexion torque variability in the anterior cruciate ligament—deficient (ACLD) leg and their dependence on muscle length and visual feedback (VF). Although a knee extension torque deficit is found in the ACLD leg, there is no evidence that variability in submaximal isometric knee extension and flexion torque is affected in the ACLD leg or that it depends on VF.     

Traditional risk factor assessment does not capture the extent of cardiovascular risk in systemic lupus erythematosus

Background: Systemic lupus erythematosus (SLE) is associated with accelerated atherosclerosis. However, the degree of endothelial dysfunction and its relationship to traditional and novel cardiovascular risk factors have not been examined in SLE. Methods: In a case–control design, 35 patients with clinically stable SLE and 35 control subjects matched for age, sex, body mass index and smoking status were studied. Arterial elasticity, lipid profile, homocysteine, measures of inflammation and oxidative stress were determined. Results: Among traditional vascular risk factors, there was a nonsignificant trend towards lower blood pressure in the control subjects, whereas low‐density lipoprotein (LDL) cholesterol levels were significantly lower in the SLE group (2.5 vs 3.3 mmol/L, P < 0.001). Patients with SLE had significantly lower small artery elasticity (SAE; 4.9 vs 7.0 ml/mmHg × 100, P < 0.001) and higher plasma homocysteine (11.4 vs 8.3 mmol/L, P = 0.002) than control subjects. Levels of serum sVCAM‐1 (614 vs 494 ng/mL, P = 0.002), oxidized LDL (144 vs 97, P < 0.001) and CD40 ligand (4385 vs 1373 pg/ml, P = 0.001) were significantly higher in SLE. Oxidized LDL levels, older age at SLE diagnosis and higher disease damage scores correlated inversely with SAE but not traditional risk factors. Conclusion: Impaired endothelial function as shown by decreased SAE, and an adverse profile of novel proatherogenic and prothrombotic vascular disease risk factors were prevalent in clinically quiescent SLE. These findings show the vulnerability of patients with SLE for atherosclerosis, and emphasize that assessments based on traditional risk factors alone may be inadequate.     

Targeting osteoclasts with zoledronic acid prevents bone destruction in collagen‐induced arthritis

Objective

To study the effect of zoledronic acid (ZA) on synovial inflammation, structural joint damage, and bone metabolism in rats during the effector phase of collagen‐induced arthritis (CIA).

Methods

CIA was induced in female dark agouti rats. At the clinical onset of CIA, rats were assigned to treatment with vehicle or single subcutaneous doses of ZA (1.0, 10, 50, or 100 μg/kg). Clinical signs in all 4 paws were scored on a daily basis. After 2 weeks, the joints in the hind paws were assessed using plain radiographs, microfocal computed tomography (micro‐CT), histologic scoring, and histomorphometry, and the serum levels of type I collagen crosslinks were measured by enzyme‐linked immunosorbent assay.

Results

Although ZA mildly exacerbated synovitis, it effectively suppressed structural joint damage. At doses of ≥10 μg/kg, ZA significantly reduced radiographic bone erosions, Larsen scores, and juxtaarticular trabecular bone loss as quantified by micro‐CT. ZA prevented increased type I collagen (bone) breakdown in CIA and diminished histologic scores of focal bone erosion by up to 80%. Increases in the percentage of eroded surface, osteoclast surface, and osteoclast numbers associated with CIA were prevented by ZA, even though synovitis scores were unchanged.

Conclusion

Single doses (≥10 μg/kg) of ZA strikingly reduced focal bone erosions and juxtaarticular trabecular bone loss, although synovitis was mildly exacerbated. Targeting osteoclasts with ZA may therefore be an effective strategy for preventing structural joint damage in rheumatoid arthritis.

     

Clinically significant metastatic melanoma to prostate

Malignant melanoma metastatic to the lower genitourinary tract is an unusual cause of urinary obstruction. It is usually a diagnosis made at autopsy. Occasionally malignant melanoma may cause significant obstructive symptoms that require intervention, although the prognosis for these patients is uniformly poor due to widespread disseminated disease.