A specific antibody and epitope binding that shows the highest affinity and is pathogenic occurs between GPA antibodies and the anti-GBM epitope region, designated EA, which is residues 17-31 of the alpha 3 subunit of non-collagenous domain of type IV collagen. T cells are also implicated, though it is generally considered a type II hypersensitivity reaction. Diagnosis
The diagnosis of GPS is often difficult, as numerous other diseases can cause the various manifestations of the condition and the condition itself is rare. The most accurate means of achieving the diagnosis is testing the affected tissues by means of a biopsy, especially the kidney, as it is the best-studied organ for obtaining a sample for the presence of anti-GBM antibodies. On top of the anti-GBM antibodies implicated in the disease, about one in three of those affected also has cytoplasmic antineutrophilic antibodies in their bloodstream, which often predates the anti-GBM antibodies by about a few months or even years. The later the disease is diagnosed, the worse the outcome is for the affected person.In addition, if there is substantial suspicion of the disease, seralogic testing for ELISA assay is usually done by looking for alpha3 NC1 domain area of collagen IV in order to avoid false positives. Treatment
The major mainstay of treatment for GPS is plasmapheresis, a procedure in which the affected persons blood is sent through a centrifuge and the various components separated based on weight. The plasma contains the anti-GBM antibodies that attack the affected persons lungs and kidneys, and is filtered out.
Scleroderma symptoms were first described in 1753 by Carlo Curzio and then well documented in 1842. The term is from the Greek skleros meaning "hard" and derma meaning "skin". Signs and symptoms
Potential signs and symptoms include:
Cardiovascular: Raynauds phenomenon (is the presenting symptom in 30% of affected persons, occurs in 95% of affected individuals at some time during their illness); healed pitting ulcers on the fingertips; skin and mucosal telangiectasis; palpitations, irregular heart rate and fainting due to conduction abnormalities, hypertension, and congestive heart failure
Digestive: gastroesophageal reflux disease, bloating, indigestion, loss of appetite, diarrhoea alternating with constipation, sicca syndrome and its complications, loosening of teeth, and hoarseness (due to acid reflux). Pulmonary: progressive worsening of shortness of breath, chest pain (due to pulmonary artery hypertension) and dry, persistent cough due to interstitial lung disease
Musculoskeletal: joint, muscle aches, loss of joint range of motion, carpal tunnel syndrome, and muscle weakness
Genitourinary: erectile dysfunction, dyspareunia, kidney problems, or kidney failure
Other: facial pain due to trigeminal neuralgia, hand paresthesias, headache, stroke, fatigue, calcinosis, and weight loss

Cause
Scleroderma is caused by genetic and environmental factors. Mutations in HLA genes seem to play a crucial role in the pathogenesis of some cases; likewise silica, aromatic and chlorinated solvents, ketones, trichloroethylene, welding fumes, and white spirits exposure seems to contribute to the condition in a small proportion of affected persons. Pathophysiology
It is characterised by increased synthesis of collagen (leading to the sclerosis), damage to small blood vessels, activation of T lymphocytes, and production of altered connective tissue.