Autoimmune Diseases and Disorders

Systemic Autoimmune Diseases

Autoimmune diseases that affect multiple systems and organs, such as Systemic Lupus Erythematosus (SLE) and Rheumatoid Arthritis (RA).

Organ-Specific Autoimmune Diseases

Autoimmune diseases that target specific organs, such as Hashimoto's thyroiditis and Type 1 diabetes.

Immunologic Tolerance

The ability of the immune system to recognize self-antigens and not mount an immune response against them.

Self-Tolerance

The capacity of the immune system to differentiate between self and non-self, preventing attacks on the body's own proteins.

Antinuclear Antibodies (ANAs)

Autoantibodies directed against antigens in cell nuclei, present in more than 95% of lupus patients.

Central Tolerance

The process of eliminating self-reactive T and B cells in the thymus and bone marrow.

Peripheral Tolerance

Mechanisms that prevent activation of self-reactive T and B cells in the peripheral immune system.

Granulomatosis with Polyangiitis (Wegner’s Granulomatosis)

A rare autoimmune disease that causes inflammation of small to medium-sized blood vessels, often affecting the respiratory tract.

Myasthenia Gravis

An autoimmune disorder that causes weakness in skeletal muscles due to antibodies blocking acetylcholine receptors at the neuromuscular junction.

Rheumatoid Arthritis (RA)

A chronic autoimmune disorder that primarily affects joints, leading to inflammation and possible deformities.

Systemic Lupus Erythematosus (SLE)

A chronic autoimmune disease characterized by a wide range of symptoms and autoantibodies affecting multiple organ systems.

Celiac Disease

An autoimmune disorder triggered by gluten in genetically susceptible individuals, leading to inflammation in the intestinal mucosa.

Hashimoto's Thyroiditis

An autoimmune disorder where autoantibodies target thyroid tissues, leading to hypothyroidism.

Graves' Disease

An autoimmune disorder characterized by the overproduction of thyroid hormones due to autoantibodies stimulating TSH receptors.

Type 1 Diabetes Mellitus

An autoimmune disorder characterized by insulin deficiency due to destruction of beta cells in the pancreas.

Anti-Glomerular Basement Membrane Disease

An autoimmune condition where antibodies target the basement membranes of the kidneys and lungs, leading to damage.

Phospholipid Antibodies

Antibodies that bind to phospholipids, associated with increased risk of thrombosis and recurrent pregnancy loss.

Autoantibodies

Antibodies that mistakenly target and react with a person's own cells or tissues.

Immunofluorescence Test (IFT)

A laboratory technique used to detect the presence of ANAs by using fluorescent labels to visualize immune complexes.

ELISA (Enzyme-Linked Immunosorbent Assay)

A common laboratory test used to detect specific antibodies in the blood.

Autoimmune diseases

humoral and cell-mediated immune responses directed toward self-antigens due to failure to recognize itself (the body)

SLE is caused by type _____ hypersensitivy reaction. Tissue damage occurs at the sites in the body where immune complexes have deposited.

3

What is the physiology behind SLE?

Immune complexes form, triggering complement activation, chemotaxis of neutrophils, and inflammation

Homogenous diffuse pattern indicates anti-_____ and the diagnoses can be _____

anti-DNA, histone, DNP; RA + SLE

Peripheral pattern indicates anti-_____ and the diagnoses can be _____

anti-DNA; SLE

Speckled pattern indicates anti-_____ and the diagnoses can be _____

Anti-SM & RNP; Anti-Ro + La, Anti-jo-1 + Mi-2, Anti-Sci; SLE, SS, PM/DM, PSS

Centromere pattern indicates anti-_____ and the diagnoses can be _____

anti-centromere; CREST

Nucleolar pattern indicates anti-_____ and the diagnoses can be _____

anti-nucleolar; SLE + PSS

SLE disnosis needs

anti-smith and anti-double-stranded DNA (anti-dsDNA)

Drug induced lupus diagnoses needs

anti-histone

Sjogren’s syndrome diagnosis needs

Anti-SS-A (Ro), anti-SS-B (La)

Mixed connective tiisue disease diagnosis needs

anti-RNPanti-U1 ribonucleoprotein antibodies

Systemic scleroderma (SS) diagnosis needs

anti-scl-70

Crithidia luciliae in IIF testing contains a kinetoplast that is rich in dsDNA to

detect antibodies to dsDNA and determine dsDNA antibody titers

ENA (Extractable Nuclear Antigens) Ouchterlony Test

is a test used to detect antibodies against a group of specific nuclear antigens

Phospholipid Antibodies bind to phospholipid and affects

platelet functionand clotting mechanisms in the body. Two types: anti-cardiolipin & Lupus-like anticoagulant

Physiology of Rheumatoid Arthritis:

immune complexes form between autoantibodies (RA & anti-CCP) and self antigen. Overly active osteoclasts absorb the bone. Involves type 3 and TNF-A

Treatment of Rheumatoid Arthritis

NSAIDS, Disease modifying anti-rheumatic drugs, agents that target TNF-A

Testing for Rheumatoid Arthritis

• Rheumatoid factor

• Anti-CCP

• ANAs

What is rheumatoid factor?

An autoantibody (usually IgM) that reacts with Fc portion of IgG

What is anti-CCP?

autoantibody directed against cyclic citrullinated peptide & is highly specific for RA

What is the ANA pattern for RA?

speckled pattern (against RNP)

Sjogren’s Syndrome

dry eyes and mouth

Systemic Sclerosis (SSc)

Fibrosis and vasculitis affecting skin, joints, and other organs (CREST)

Mixed connective tissue disease

overal of limited utaneous SSc and other systemic autoimmune rheumatic diseases

Inflammatory myopathies

polymyositis and dermatomyositis, progressive muscle weakness

Wegner’s Granulomatosis patients have anti-____

anti-neutrophil cytoplasmic antibodies, which are detected by IIF

Wegner’s Granulomatosis physiology

neutrophil activation results in damage to vascular endothelium and a Th1 response

Hashimoto’s thyroiditis has autoantibodies to

TG and TPO leading to a decrease in thyroid hormone synthesis.

Lab results of Hashimoto’s is

• high or normal TSH

• Low free T4, T3

• Anti-TPO

• Anti-TG

Grave’s Disease has autoantibodies that

bind to TSH receptors, mimicking TSH action, but excessively increase thyroid hormone synthesis by bypassing the thyroid axis

Grave’s Disease lab results

• TSI (thyroid-stimulating immunoglobulin), Anti-TSH

• Low TSH

• High total and free T4, T3

T1 DM physiology

Autoantibodies destroy beta cells through CD-8 cell response. Cytokines are released + progressive inflammation

Type 1 DM Lab results

• increase blood glucose

• Elevated HbA1c

• Autoantibodies to Glutamic acid decarboxylase-65 antigen (GAD), insulinoma antigen 2 (IA-2), and islet cell antibodies (ICA)

Celiac Disease physiology

Gliadin in gluten is processed by APCs + interact with CD4 T cells, triggering inflammation (IgA involved)

Celiac testing tests for

Autoantibodies from HLA-DQ-2 or HLA-DQ8

Autoimmune Liver Disease symptoms

elevated liver enzymes, fatigue, nausea/vomiting, abdominal pain, itchy skin, jaundice

Type AIH-1 and AIH-2

Autoimmune hepatitis 1 (AIH-1)

posive for smooth muscle antibodies or ANAs

Autoimmune hepatitis 2 (AIH 2)

Positive for Liver-kidney microsomal antibodies (LKM-1) or Liver cytosol type 1 antibodies (LC-1)

Primary biliary cholangitis (PBC) is the

destruction of intrahepatic bile ducts, where bile flow is slowed or blocked. Suspected when no other risk factors for chronic liver disease

Primary biliary cholangitis patients produce anti-

anti-mitochondrial antibodies, detected by IIF

Anti-glomerular basement membrane disease (Goodpasture’s syndrome) affects

pulmonary and renal systems

Goodpasture’s syndrome patients produce

autoantibodies to basement membranes lining the renal glomeruli and lung alveoli

Goodpasture physiology

immune complexes bind to basement membranes, attract complements, and cause damage by type 2 hypersensitivity

Multiple Sclerosis involves inflammation and destruction of the

CNS; and is characterized by lesions called plaques that form in white matter of brain/spinal cord

Multiple sclerosis patients produce antibodies against

myelin basic protein

Multiple sclerosis lab findings

• lesions seen on MRI

• Increased IgG/albumin and antiboides in spinal fluid

• Oligoclonal bands on electrophoresis

Myasthenia Gravis affects

the neuromusclar junction, resulting in weak skeletal muscles

Myasthenia Gravis patiens have antibodies to

Acetylcholine (ACH) receptors on skeletal muscles at the neuromusclar junction. Autoantibodies block ACH binding and transmission of nerve impulses, so neuron fails to signal