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Organ-specific autoimmune diseases

Organ-specific autoimmune diseases

Organ-specific autoimmune diseases

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Endocrine Autoimmunity - Hormonal Havoc

Pathogenesis of Autoimmune Thyroid Diseases

  • Hashimoto's Thyroiditis (Hypothyroidism):

    • Antibodies: Anti-thyroid peroxidase (anti-TPO), anti-thyroglobulin.
    • Mechanism: CD8+ T-cell cytotoxicity & antibody-mediated destruction of follicular cells.
    • Pathology: Lymphocytic infiltrate with germinal centers; Hürthle cell metaplasia.
  • Graves' Disease (Hyperthyroidism):

    • Antibody: Thyroid-Stimulating Immunoglobulin (TSI), a TSH-receptor antibody.
    • Mechanism: Type II hypersensitivity where antibodies stimulate the TSH receptor, leading to ↑T3/T4.
  • Type 1 Diabetes Mellitus:

    • Antibodies: Anti-GAD65, islet cell autoantibodies.
    • Mechanism: T-cell mediated destruction of pancreatic β-cells.

⭐ Graves' disease exophthalmos is caused by T-cell infiltration and fibroblast proliferation in orbital tissues, not by direct thyroid hormone effects.

GI & Hematologic - Gut Feelings

  • Celiac Disease
    • Patho: Immune response to gluten (gliadin) in genetically susceptible individuals (HLA-DQ2/DQ8).
    • Antibodies: IgA anti-tissue transglutaminase (tTG), anti-endomysial, anti-deamidated gliadin peptide.
    • Histo: Villous atrophy, crypt hyperplasia, intraepithelial lymphocytes.
  • Pernicious Anemia
    • Patho: Autoimmune gastritis; T-cell mediated destruction of gastric parietal cells.
    • Antibodies: Anti-parietal cell, anti-intrinsic factor (more specific).
    • Effect: ↓ Intrinsic factor → Vitamin B12 deficiency → Megaloblastic anemia.

⭐ Dermatitis herpetiformis (pruritic papules/vesicles on extensor surfaces) is the specific skin manifestation of Celiac Disease.

Celiac Disease: Villous Atrophy vs. Normal Mucosa

Neurologic Syndromes - Nerve-Wracking

  • Multiple Sclerosis (MS): Central (CNS) demyelination.

    • Autoimmune T-cell response to myelin basic protein. Type IV HSR.
    • Sx: Optic neuritis, internuclear ophthalmoplegia (INO), sensory deficits separated in time & space.
    • Dx: ↑ IgG (oligoclonal bands) in CSF, periventricular plaques on MRI.
  • Myasthenia Gravis (MG): Peripheral (PNS) neuromuscular junction.

    • Autoantibodies to postsynaptic ACh receptors. Type II HSR.
    • Sx: Ptosis, diplopia, muscle weakness worsening with use.
  • Guillain-Barré Syndrome (GBS): PNS demyelination.

    • Molecular mimicry (often post-Campylobacter jejuni).
    • Sx: Symmetric ascending paralysis/weakness.

Myasthenia Gravis is strongly associated with thymoma or thymic hyperplasia (~75% of cases).

Neurological manifestations of autoimmune diseases

Dermatologic Issues - Skin Deep Trouble

  • Pemphigus Vulgaris vs. Bullous Pemphigoid: Autoimmune blistering diseases differentiated by the level of skin separation.
FeaturePemphigus VulgarisBullous Pemphigoid
AntigenDesmoglein 1 & 3 (in desmosomes)Hemidesmosomal proteins
Blister LevelIntraepidermalSubepidermal
ClinicalFlaccid, easily ruptured bullae; oral mucosa common; + Nikolsky signTense bullae; oral mucosa rare; - Nikolsky sign
IF PatternReticular (net-like)Linear at dermal-epidermal jxn

Exam Favorite: Oral mucosal involvement is common in Pemphigus Vulgaris and rare in Bullous Pemphigoid, a key clinical differentiator.

📌 Mnemonic: Bullous is Below the epidermis (subepidermal) and blisters are Bound-down and tense.

High‑Yield Points - ⚡ Biggest Takeaways

  • Hashimoto's thyroiditis: Anti-TPO & anti-thyroglobulin Abs lead to hypothyroidism.
  • Graves' disease: Thyroid-stimulating immunoglobulin (TSI) causes hyperthyroidism.
  • Type 1 Diabetes: T-cell mediated destruction of pancreatic β-cells.
  • Myasthenia Gravis: Antibodies block postsynaptic ACh receptors at the NMJ.
  • Goodpasture Syndrome: Abs against Type IV collagen in kidney & lung basement membranes.
  • Pernicious Anemia: Anti-intrinsic factor Abs cause vitamin B12 deficiency.

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Practice Questions: Organ-specific autoimmune diseases

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A 34-year-old woman comes to the physician because of a 3-month history of fatigue and a 4.5-kg (10-lb) weight loss despite eating more than usual. Her pulse is 115/min and blood pressure is 140/60 mm Hg. Physical examination shows warm, moist skin, and a diffuse, non-tender swelling over the anterior neck. Ophthalmologic examination shows swelling of the eyelids and proptosis bilaterally. Which of the following is the most likely cause of this patient's symptoms?

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Flashcards: Organ-specific autoimmune diseases

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In Celiac disease, _____ is presented by APCs via MHC class II

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In Celiac disease, _____ is presented by APCs via MHC class II

deamidated gliadin

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