autoimmune diseases related to hematology Flashcards
a consequence of long standing gastritis leading to atrophy of all the cells of the stomach (secretory).
Pernicious Anaemia
Autoimmune gastritis (AIG) is an organ-specific inflammatory
disorder leading
gastric atrophy & pernicious anemia.
Pathogenesis of AIG: caused by () with specificity for the () of the parietal cell proton pump () located in parietal cells of gastric mucosa. Gastric T cell recognition of the peptide epitopes results in secretion of ()
CD4+ T cells
beta sub-unit
(H+ /K+ ATPase)
TH1 cytokines.
Inflammation of gastric mucosa results in loss of parietal cell function 4 points
1- hydrochloric acid & intrinsic factor secretion;
2- iron deficiency,
3- vitamin B12 deficiency (some casespernicious anaemia);
4- gastric atrophy.
Pernicious Anaemia (PA) AutoimmuneFeatures
1- Anti–parietal cell antibodies
2- Anti–intrinsic factor antibodies
Anti–parietal cell antibodies
react with gastric parietal cells and are present in >90% of patients
major antigen for α-Parietal cell Abs
The acid-producing enzyme H+/K+-ATPase (92-kDa protein) present on the luminal membrane of parietal cells
occur in the serum, saliva, and gastric juice of 50-75% of patients with PA.
Anti–intrinsic factor antibodies
Pernicious Anemia is more common in individuals with
other autoimmune disease, especially polyglandular autoimmune syndromes, (e.g., Hashimoto’s thyroiditis, Graves’ disease, vitiligo, diabetes mellitus & Addison’s Disease).
acquired disorder characterized by isolated thrombocytopenia due to pathogenic anti-platelet antibodies
Immune Thrombocytopenia (ITP)
Acute ITP
usually self-limited occurring 1-3 weeks after a viral infection (e.g., nonspecific upper respiratory or gastrointestinal tract, rubella or chickenpox). Abrupt onset of bruising petechiae &/or epistaxis in previously healthy children is characteristic.
Chronic ITP
↑ incidence in females. Presenting symptoms include mucocutaneous bleeding, with menorrhagia, recurrent epistaxis & easy bruising.
mainly due to IgG autoantibodies which bind to platelets and megakaryocytes (MKs), targeting very abundant surface Ags such as glycoprotein (GP) αIIbβ3 (GPIIb/IIIa) and GPIb−IX.
Itp
Platelets with bound autoantibodies are subsequently recognized by () -> enhanced Ab-mediated platelet phagocytosis & removal from circulation ()
phagocytes bearing FcγRs
by reticuloendothelial cells (mainly in spleen).
Direct lysis of platelets by () has been detected along with an ↑ () cytokines & ↓ (_)
cytotoxic T lymphocytes (CTLs)
TH1/TH17
Tregs
Autoantibody binding to MKs & CTLs can lead to
deficiency in platelet release.
Many drugs can induce acute thrombocytopenia including
analgesics, antibiotics & sedatives.
Platelets: Common mechanism involves Ig binding () by their Fab (Ag-binding) region. () bind the Fc portion of the Ig. This may result in (_)
a platelet membrane Ag or Ag-drug combination
M⍬ Fc receptors
platelet removal & thrombocytopenia
Heparin-Induced Thrombocytopenia is mediated
by FcγRIIa
IgG autoantibodies that recognize PF4 in complex with heparin
FcRIIa.
Ig Fc domains within the immune complex bind to the platelet receptor FcγRIIa, and activate platelets leading to
platelet aggregation (thrombosis) & clearance
Rare disorder characterized by premature RBC destruction and anemia caused by autoantibodies that bind the RBC surface with or without complement activation
Autoimmune Hemolytic Anemia (AIHA)
the severity of Autoimmune Hemolytic Anemia (AIHA) depends on:
Characteristics of AutoAb (titer, ability to react at 37oC, ability to activate complement, and specificity & affinity for the autoAg).
Ag characteristics (density on RBCs, immunogenicity)
Patient related factors (age, B.M. compensation ability, M⍬ functionality, complement function/regulation)
erythrocytes are destroyed in the blood vessel itself
Intravascular Hemolysis
occurs in the hepatic & splenic macrophages within the
reticuloendothelial system
Extravascular Hemolysis
in AIHA Autoantibodies my arise due to:
immune dysregulation & loss of
immune tolerance
exposure to an Ag similar to an autoAg B lymphocyte neoplasm
unknown reason (idiopathic).
what can influence the development of autoAbs
The amount, type, duration of Ag exposure, in addition to genetic & environmental factors
AIHA may be divided into four major categories:
Warm AIHA
Cold agglutinin disease
Paroxysmal cold hemoglobinuria
Mixed-type AIHA
the most common type of AIHA comprising up to 70% of AIHA cases.
Warm Autoimmune Hemolytic Anemia (WAIHA)
Most of these Abs are of IgG class, rarely IgA or IgM
Warm Autoimmune Hemolytic Anemia (WAIHA)
Secondary WAIHA could be in conditions such as:
Lymphoproliferative diseases
Non-lymphoid neoplasms
Autoimmune disorders Immunodeficiency disorders
Viral infections
comprises approximately 1⁄4 of AIHA cases.
Cold Agglutinin Disease (CAD)
autoAb IgM that react optimally at 4oC.
CAD
nonpathogenic cold agglutinins
polyclonal, occur in low titers & have no reactivity > 30oC.
(healthy individuals)
Pathogenic cold agglutinins are
monoclonal, occur in high titers &
are capable of reacting at temperatures > 30oC -> can induce CAD.
chronic cad
idiopathic or secondary to lymphoproliferative neoplasms
acute CAD
occurring secondary to Mycoplasma pneumoniae infections, infectious mononucleosis or other viral infections
IgM autoAb bind RBCs after exposure to cold
In CAD,
The immune hemolysis is entirely complement-dependent.
CAD
an acute form of cold-reactive hemolytic anemia.
Paroxysmal Cold Hemoglobinuria (PCH)
most commonly seen in young children after respiratory viral infections & has childhood incidence as high as 32- 40% of children with autoimmune hemolytic anemia (5 yr median). rare in adults
Secondary PCH
Paroxysmal Cold Hemoglobinuria (PCH) mechanism
Anti-P autoAb can bind to P Ag on RBCs & partially activate complement (C1-C4) at cold temperatures & upon warming to 37oC, full complement activation (C3 through C9) and hemolysis occur
special feature of PCH
Exposure to cold temperatures is NOT required for hemolytic manifestations.
what is mainly associated with SLE & lymphoma.
Mixed-Type AIHA
Patients simultaneously develop IgG autoAb with optimum reactivity at 37oC (WAIHA) and IgM autoAb that react optimally at 0-10oC but have thermal amplitude of >30oC (CAD).
Mixed-Type AIHA
Mixed-Type AIHA Hemolysis results from
a combination of extravascular & intravascular mechanisms.
The warm autoAb are typically () with unclear specificity & the cold-reacting autoAb usually have ()specificity.
panreactive
anti-I
which type of AIHA presents with a course that appears to be chronic with intermittent episodes of severe anemia.
Mixed-Type AIHA
