====== Immunoglobulin G4 (IgG4) ======

Immunoglobulin G4 (IgG4) is one of the four subclasses of immunoglobulin G (IgG), representing less than 5% of total serum IgG in healthy individuals. It plays a unique role in immune regulation and is notably implicated in IgG4-related disease (IgG4-RD).

===== Basic Properties =====
  * Molecular weight: ~150 kDa
  * Serum concentration: 0.05–1.5 g/L
  * Comprises <5% of total IgG
  * Half-life: ~21 days
  * Poorly activates complement via the classical pathway

===== Structural Characteristics =====
  * Fab-arm exchange: IgG4 molecules can exchange half-molecules, leading to functionally monovalent antibodies
  * Low affinity for Fc receptors and C1q → reduced pro-inflammatory activity

===== Functional Role =====
  * Generally considered anti-inflammatory
  * Acts as a "blocking antibody" in allergy desensitization therapy
  * May downregulate immune responses by competing with other IgG subclasses

===== Clinical Relevance =====

==== ↑ Elevated IgG4 levels observed in: ====
  * IgG4-related disease (IgG4-RD)
  * Atopic dermatitis
  * Parasitic infections
  * Certain cancers (e.g., pancreatic)
  * Chronic inflammatory diseases (non-specific)

==== ↓ Low IgG4 levels: ====
  * Often not clinically significant unless associated with other immunoglobulin deficiencies

===== Measurement =====
  * Serum IgG4 quantification by nephelometry or ELISA
  * Used in diagnosis and monitoring of IgG4-RD, but not diagnostic alone

===== In IgG4-Related Disease (IgG4-RD) =====
  * Elevated serum IgG4 in ~60–70% of cases
  * Tissue infiltration with IgG4+ plasma cells is key for diagnosis
  * Not all patients with elevated IgG4 have IgG4-RD, and vice versa

===== Differential Diagnosis for Elevated IgG4 =====
  * [[Immunoglobulin G4-related disease]]
  * Allergic diseases
  * Parasitic infections
  * Multicentric Castleman disease
  * Autoimmune pancreatitis
  * Chronic sinusitis