Multiple Sclerosis Patients with Markedly Low Intrathecal Antibody Response in Sri Lanka.

Multiple sclerosis (MS) is a heterogeneous disease which is poorly studied in Asia, where the disease is known to be rare with significant differences in clinical and radiological presentations and intrathecal antibody response. Therefore the objective of this study was to determine clinical presentation, radiological and neurophysiological characteristics, and oligoclonal band status in Sri Lankan MS patients, following careful exclusion of patients with neuromyelitis optica spectrum disorders and other conditions mimicking multiple sclerosis. Sixty-nine MS patients were recruited to the study adhering to McDonald 2010 criteria. Their clinical presentation, characteristics of central nervous system lesions in magnetic resonance imaging, visual evoked potential (VEP) results, oligoclonal bands (OCB), and AQP4 antibody status were studied. Of 69 MS patients, 54%, 6%, and 1% were relapsing remitting, secondary progressive, and primary progressive, respectively, and 39% were patients with clinically isolated syndrome. The commonest clinical presentations were cerebral motor followed by cerebral sensory and optic neuritis. Majority had typical periventricular and infratentorial lesions in MRI. Though not clinically apparent, bilateral delay of P100 wave latency was present in 52%. OCB positivity was 42% and AQP4 antibody was positive in only one patient. In conclusion, this group of Sri Lankan MS patients shares most of the clinical and radiological features of Caucasian MS patients. However, the OCB positivity is lower in this group, when compared to the Caucasian MS populations.

Relationship between the goniometric alignment and articular cartilage damage in knee osteoarthritis

Introduction: Osteoarthritis of the knee is common among the elderly. The alignment of the knee plays an important part in disease progression. Objectives: The aim was to determine the relationship between goniometric measurement of malalignment and gross and histological damage to articular cartilages of osteoarthritic knees. Methods: Anterior plane knee alignment was measured using a handheld metal goniometer in 84 patients awaiting knee replacement. Articular cartilages removed at surgery were stained and examined for macroscopic and microscopic damage which were quantified with macroscopic visual assessment score and Mankins histochemical score, respectively. The relationship between the type of knee angulation and macroscopic and microscopic damage to medial and lateral compartments was analyzed using analysis of variance (ANOVA), and the relationship between the degree of angulation and the degree of damage was determined using multiple linear regression models. Results: Varus knees had markedly higher macroscopic damage scores in the medial than the lateralcompartment (p<0.0001), while valgus knees showed the opposite (p<0.0001). The knee angulation, together with age and BMI, predicted 54% of the macroscopic (p<0.0001) and 60% of the microscopic damage (p<0.0001) in varus knees. Conclusions: Anterior plane goniometric knee alignment is a significant predictor of the articular cartilage damage present in an osteoarthritic knee. Goniometric measurement is a valuable tool in assessing the disease severity as it is a simple, safe and cost-effective method.

Goniometric alignment of the normal knee joint and the factors which affect it.

OBJECTIVES: Establishing a normative database for anterior plane knee joint alignment in a population is helpful in assessing patients with disorders of the knee joint specially osteoarthritis. Therefore we aimed at establishing the normal alignment in the Sri Lankan adult population using the goniometer which is an inexpensive and simple method of measurement. METHODS: A total of 420 healthy adult volunteers (210 men and 210 women) above 25 years of age were recruited and the anterior plane knee alignment was measured using a hand held metal goniometer. RESULTS: The mean knee joint alignment was 180.56° (SD 2.39) and 183.04° (SD 2.34) in males. The knee joints of the females were varus-oriented by, 2.48° than those of males (p< 0.0001). In the females the knee joint alignment showed a gradually varus inclination with increasing age (p< 0.05). Lifting heavy weights in males caused a significant varus inclination of the knee joint while BMI and squatting for long periods did not have an effect on the normal alignment. CONCLUSIONS: Female knees are more varus inclined than that of males in the Sri Lankan participants and this inclination increases with age. Reasons for this could be genetic and lifestyle differences and may partly explain the reason for the predominance of varus osteoarthritis in Sri Lankan females.

Interferon-gamma-modified dendritic cells suppress B cell function and ameliorate the development of experimental autoimmune myasthenia gravis.

This study was designed to investigate the therapeutic effects of interferon (IFN)-gamma-modulated dendritic cells (DC) in experimental autoimmune myasthenia gravis (EAMG). We induced EAMG in Lewis rats by immunization with Torpedo nicotinic acetylcholine receptor (nAChR) and adjuvant. On day 33 post-immunization (p.i.), splenic DC were prepared, exposed to IFN-gamma alone (IFN-gamma-DC) or to IFN-gamma in combination with 1-methyl-DL-tryptophan (1-MT), the specific inhibitor of indoleamine 2,3-dioxygenase (IDO) (IFN-gamma + 1-MT-DC), and injected subcutaneously into rats with incipient EAMG on day 5 p.i. A control group of EAMG rats received naive DC on day 5 p.i., while another group received 1-MT every other day, intraperitoneally (p.i.), from days 5 to 41 p.i. The severity of clinical signs of EAMG was reduced dramatically in IFN-gamma-DC-treated rats compared to rats receiving naive DC, IFN-gamma + 1-MT-DC or 1-MT alone. The number of plasma cells secreting nAChR antibodies was reduced and the expression of B cell activation factor (BAFF) on splenic and lymph node mononuclear cells (MNC) was down-regulated in rats treated with IFN-gamma-DC. In vitro co-culture of MNC derived from EAMG rats with IFN-gamma-DC produced relatively few cells secreting nAChR antibodies. Addition of 1-MT to the co-culture significantly increased the number of cells secreting nAChR antibodies. We conclude that IFN-gamma-DC reduced the number of plasma cells secreting nAChR antibodies in an IDO-dependent manner and ameliorated the development of EAMG in Lewis rats.

Interleukin-10-modulated immature dendritic cells control the proinflammatory environment in multiple sclerosis.

Multiple sclerosis (MS) is a disabling, inflammatory, demyelinating disease of the central nervous system considered to be mediated by autoreactive T cells. Dendritic cells (DC), being professional antigen-presenting cells, play a pivotal role in the decision between T-cell activation and anergy. It has been suggested that mature DC (mDC) induce immunity, whereas immature DC (imDC) have the potential to induce tolerance. In this study, we investigated the effects of autologous imDC versus autologous mDC on lymphocytes with respect to the expression of functionally important cell-surface molecules and production of cytokines. Our aims were to investigate whether the maturation status of DC differs between MS and healthy controls (HC) and to explore whether the effects of DC on T-cell responses differ between MS and HC. DC were generated from adherent blood mononuclear cells from patients with MS and HC. imDC were obtained by culture with either granulocyte-macrophage colony-stimulating factor (GM-CSF) + interleukin-4 (IL-4) or GM-CSF + IL-4 + IL-10. mDC were obtained by adding lipopolysaccharide to DC cultures. Upon coculture with autologous lymphocytes, mDC activated the autologous T cells as reflected by increased CD25 and cytotoxic T-lymphocyte antigen-4 expression on CD4(+) T cells together with the increased production of both T helper 1 (Th1) (IL-2 and interferon-gamma) and Th2 (IL-10 and IL-4) cytokines. Unmodulated naïve imDC induced the production of only IL-4. An exposure of imDC to IL-10 induced the production of IL-4 as well as IL-10 by autologous lymphocytes. We hypothesize that such imDC are important in controlling the proinflammatory environment in vivo in patients with MS.