Lupus

Lupus is a difficult disease to diagnose, & can be overlooked, often for years, unless the GP or consultant is alert to it's possibilities.

To help distinguish Lupus from other diseases, physicians of the American Rheumatism Association have established a list of 11 abnormalities which, when combined, point to lupus. To make a diagnosis of Lupus the patient must have had at least FOUR of these 11 manifestations at any time since the onset of the disease.

1	Malar rash	fixed red rash over the cheeks
2	Discoid rash	red patches of skin associated with scaling and plugging of the hair follicles
3	Photosensitivity	rash after exposure to sunlight
4	Mucosal ulcers	small sores that occur in mucosal lining of mouth and nose
5	Serositis	inflammation of the delicate tissues covering internal organs and abdominal pain
6	Arthritis	-very common in lupus, pain in the joints
7	Renal disorders	usually detected by routine blood and urine analysis
8	Neurological disorder	seizures or psychosis
9	Haematological disorder	haemolytic anaemia, leukopenia, thrombocytopenia
10	Immunologic disorder	tests on LE cells, anti-DNA and anti-SM antibodies
11	Anti-Nuclear Antibody (ANA blood test)	when found in the blood and the patient is not taking drugs, it is known to cause a positive test for lupus in most cases, but is not necessarily conclusive

The above criteria were laid down by the ACR in 1982. Dr Graham Hughes (St. Thomas' Hospital, London)

Full Blood Count (FBC) - Detects anaemia, low platelets, low white blood cells

Creatinine and electrolytes - Measures the salts in the blood and gives an idea of kidney function

Liver function tests - Includes measurement of liver enzymes (indicator of liver cell damage). Measures albumin (marker of kidney problem with leakage of the proteins)

ESR (Erythrocyte Sedimentation Rate) - A marker of non-specific inflammation, tends to be raised in lupus CRP (C-reactive protein) - Another inflammatory marker, but this does NOT usually go up in Lupus

Urine - Measure protein and blood cells in urine (should be none). Identify ‘casts’ (blobs of protein escaped from the bloodstream because the kidneys are leaky)

Blood clotting tests - Tell how ‘sticky’ the blood is. Includes ‘lupus anti-coagulant’

Mirac stops the production of cells that cause Lupus. Lupus is caused by Natural Killer (NK) CD4 double negative and CD8 double negative T-Lymphocytes, also called T cells. These T cells multiply using a potassium gene channel. These same cells cause Diabetes. (Eur J Immunol. 1990 Apr;20(4):747-51. Autoimmune diseases linked to abnormal K+ channel expression in double-negative CD4-CD8- T cells. Chandy KG, Cahalan MD, Grissmer S. Department of Medicine, University of California, Irvine) By blocking this gene channel, Mirac stops the proliferation of cells that cause Lupus. ("Defining the Molecular Targets ....." A Research Proposal Submitted to BioSTAR Michael D. Cahalan, K. George Chandy, Department of Physiology and Biophysics, UCI, Irvine CA)

Lupus is a chronic, autoimmune disease that causes inflammation of various parts of the body, especially the skin, joints, blood, and kidneys. The body's immune system normally makes proteins called antibodies to protect the body against viruses, bacteria, and other foreign materials. These foreign materials are called antigens. In an autoimmune disorder such as lupus, the immune system loses its ability to tell the difference between foreign substances (antigens) and its own cells and tissues. The immune system then makes antibodies directed against "self." These antibodies, called "auto-antibodies," react with the "self" antigens to form immune complexes. The immune complexes build up in the tissues and can cause inflammation, injury to tissues, and pain.

Estimates indicate that between 1,400,000 and 2,000,000 people have been diagnosed with lupus. For most people, lupus is a mild disease affecting only a few organs. For others, it may cause serious and even life-threatening problems. Thousands of Americans die each year from lupus-related complications.

Biol Pharm Bull. 2000 Jan;23(1):27-32. Biochemical characterization of 60S acidic ribosomal P proteins from porcine liver and the inhibition of their immunocomplex formation with sera from systemic lupus erythematosus (SLE) patients by glycyrrhizin in vitro.

Maekawa T, Kosuge S, Karino A, Okano T, Ito J, Munakata H, Ohtsuki K. Laboratory of Genetical Biochemistry, School of Allied Health Sciences, Kitasato Unsiversity, Sagamihara, Japan.

The three casein kinase II (CK-II) phosphate acceptors (p35, p17 and p15) in the Superdex CK-II fraction prepared from a 1.5 M NaCl extract of porcine liver were selectively purified by glycyrrhizin (GL)-affinity column chromatography (HPLC) as a heterocomplex associated with CK-II. Determination of the N-terminal amino acid sequences and immunological tests confirmed that these three CK-II phosphate acceptors belong to the family of 60S acidic ribosomal proteins (P0, P1 and P2). Three polyphenol-containing anti-oxidant compounds [catechin, epigallocatechin gallate (EGCG) and quercetin] inhibited CK-II activity (phosphorylation of these ribosomal P proteins) in a dose-dependent manner in vitro. Quercetin (ID50 = approx. 50 nM) was found to be an effective CK-II inhibitor. In contrast, CK-II activity was significantly stimulated by lower doses (0.3-3 microl) of GL, but was inhibited at high doses above 30 microM. As expected, GL at high doses above 200 microM inhibited the immunocomplex formation of 60S acidic ribosomal P proteins with their specific antibodies in the sera from patients with systemic lupus erythematosus (SLE). These results suggest that (i) a GL-affinity column is useful for effective purification of 60S acidic ribosomal P proteins from various mammalian cells as a heterocomplex associated with CK-II; and (ii) a relative high dose of GL may prevent the immunocomplex formation of 60S acidic ribosomal P proteins with their specific antibodies in the sera of SLE patients.