Autoimmune Disease Flashcards
What are autoimmune diseases caused by? Are they rare or common?
- caused by immune reactions against self
- They affect at least 1% to 2% of the U.S. population
Generally 3 characteristics are needed to classify a disease as being of autoimmune etiology. What are they?
- The presence of an autoimmune reaction
- Evidence that such a reaction is not secondary to tissue damage. (resulting from infection, but is of primary pathogenetic significance)
- The absence of another well-defined cause of the disease.
The autoimmune disorders form a spectrum. What is on each end of the spectrum?
- on one end of which are conditions in which the immune response is directed against a single organ or tissue, resulting in organ-specific disease
- on the other end are diseases in which the autoimmune reaction is against widespread antigens, resulting in generalized or systemic disease
Be able to give some examples of organ specific autoimmune diseases
- Hashimoto thyroiditis
- Autoimmune hemolytic anemia
- Autoimmune atrophic gastritis of pernicious anemia
- Multiple sclerosis
- Autoimmune orchitis
- Goodpasture syndrome
- Autoimmune thrombocytopenia
- Type 1 diabetes mellitus
- Myasthenia gravis
- Graves disease
Be able to give some examples of systemic autoimmune diseases
- Systemic lupus erythematosus (SLE)
- Rheumatoid arthritis (RA)
- Sjögren syndrome (SS)
- Scleroderma (systemic sclerosis)
- Reiter syndrome
What are the two major forms of Lupus erythematous? What is the 3rd form?
- Systemic lupus erythematosus (SLE)
- Cutaneous lupus erythematosus (CLE)
- Discoid lupus erythematosus (DLE)
Cutaneous lupus erythematosus (CLE) can be divided into 3 main subtypes. What are they?
acute, subacute, and chronic
What is Discoid lupus erythematosus (DLE)
is a common form of chronic cutaneous lupus erythematosus
When does Discoid lupus erythematosus (DLE) occur?
in the absence of systemic disease, or it may occur in association with (progression to) SLE
The risk of progression to SLE in patients with DLE is 16.7% within ____ years of diagnosis according to a 2011 study.
3
Drug-induced lupus erythematosus has many features in common with SLE and characteristically develops in people who have ______________
no history of systemic autoimmune disease
the drugs with the highest risk for drug-induced lupus erythematosus are what
Procainamide and hydralazine;
incidences of ~ 20% for procainamide and 5 - 8% for hydralazine
Systemic lupus erythematosus (SLE) is the prototypical multisystem autoimmune disease characterized by the production of what?
numerous autoantibodies, especially antinuclear antibodies (ANAs)
What is the peak incidence age for Systemic lupus erythematosus (SLE)
15% - 17% of SLE cases occur prior to the age of 16 years, with the peak incidence being in the age range of 20 to 40 years
SLE occurs ____ times more frequently in females age 17 to 55 years, and has a ___ times higher prevalence among blacks and Hispanics than in whites
- 9
- 2 to 3
What is the etiology of systemic lupus erythematosus (SLE)
the specific etiology of SLE is still not known with certainty, but immunocomplexes, autoantibodies, and genetic, infectious, environmental, and endocrine factors play significant roles
The fundamental systemic pathologic mechanism in SLE is a failure to maintain ______, leading to the production of a large number of autoantibodies (e.g., ANAs) that can damage tissues secondary to _________
- immunological self-tolerance
- immune complex deposition
The fundamental pathologic mechanism (production of lots of autoantibodies) features of systemic lupus erythematosus are consistent with what type of hypersensitivity reaction?
consistent with a type III hypersensitivity reaction directed against the affected tissues and organs
In systemic lupus erythematosus (SLE), autoantibodies specific for red blood cells, white blood cells, and platelets opsonize these cells and promote their phagocytosis, resulting in cytopenias. What type of hypersensitivity is this?
These features are consistent with a type II hypersensitivity reaction directed against blood cells
The formation of autoantibodies in patients with SLE is thought to be related to what?
decreased functioning of suppressor T-cells and hyper-(auto)reactive B-cells
Immunocomplexes, consisting chiefly of ______ and _____ antibody, account for the majority of the tissue damage seen in SLE
- nucleic acid
- IgG
Immunocomplexes in SLE set off immunologic reactions that activate _____ and attract _______
- complement
- neutrophils and macrophages.
What is the result of immunocomplexes being formed in SLE?
- The result is vasculitis, fibrosis, and tissue necrosis
- Severe disease, especially affecting the kidney
- Immunocomplexes also account for tissue damage in the central nervous system, skin, and lungs
What are genetic factors of SLE?
- Familial association
- HLA association
- Other genes (genetic deficiencies)
How are familial associations a genetic factor for SLE?
- Family members have an increased risk for the development of SLE, and up to 20% of clinically unaffected first-degree relatives may have autoantibodies.
(There is a high rate of concordance in monozygotic twins (25%) versus dizygotic twins (1% to 3%))
How are HLA associations a genetic factor for SLE?
The odds ratio (relative risk) for persons with HLA-DR2 or HLA-DR3 is 2 to 3, and if both haplotypes are present, the risk is about 5.
What are environmental factors of SLE?
- Ultraviolet (UV) radiation (sun exposure)
- Cigarette smoking
SLE is _____ times more common in women during reproductive years than in men of similar ages but only ____ times more common in women during childhood or after the age of 65
- 10
- 2 to 3
How do Infectious (Viral) Factors play a role in patients with SLE?
- Virus-like particles of RNA viruses have been detected in tissues of SLE patients and are thought by some to initiate the abnormal immune response
- EBV, CMV, and VZV may have increased frequency
What are some Immunologic Abnormalities in SLE?
- Type 1 interferons
- Toll-like receptor (TLR) signals
- Failure of B cell tolerance
How are Type 1 interferons affected in SLE?
Blood cells in patients with SLE show a striking molecular signature that indicates exposure to IFN-α; patients with SLE may also produce abnormally large amounts of IFN-α
How are Toll-like receptor (TLR) signals affected in SLE?
TLRs that recognize DNA and RNA, notably the DNA recognizing TLR9 and the RNA-recognizing TLR7, produce signals that activate B cells specific for self nuclear antigens
Defects in both central and peripheral B cell tolerance result in a higher frequency of _____ cells in patients with SLE
autoreactive B
SLE is a disease with ______ involvement. There is no typical pattern of presentation
multiorgan
In SLE, Kidney involvement in the form of _____ is seen in ~ 50% of patients (and is termed _______)
- glomerular destruction
- lupus nephritis
What does lupus nephritis result from? How many patterns are there?
- from the deposition of complement and immunocomplexes in the basement membrane of the glomerulus
- Six patterns are recognized in the currently accepted classification system
5 - 22% percent of SLE patients progress to advanced sclerosing lupus nephritis (class VI) which represents what?
end-stage renal disease and requires hemodialysis or transplantation
What results from massive renal destruction and is a common cause of death in SLE patients.
Nephrotic syndrome
_______ is the most common form of lupus nephritis
Diffuse lupus nephritis (class IV)
Accelerated atherosclerosis with ______ is an important cardiac clinical problem in patients with SLE
coronary artery disease
What cardiac manifestations do women with SLE have a significantly increased risk for?
– myocardial infarction (MI) [8.5 times]
– heart failure [13.2 times]
– stroke [10.1 times] than the general population
T/F Cardiac arrhythmias are common in patients with SLE
True
______ may result from myocarditis and hypertension in patients with SLE
Heart failure
Cardiac _____ abnormalities are found in 25 - 50% of patients who have SLE.
valvular
What does the most common of all cardiac lesions in SLE patients involve? How was it originally described
the endocardium and was originally described (by Libman and Sacks) as verrucous valvular lesions (vegetations)
What are Libman-Sacks (verrucous valvular) vegetations
- Most frequently affect the mitral valve, but may occur on any valve or even on endocardial surfaces
- Represent an increased risk for the development of bacterial endocarditis
The primary hematologic diseases among SLE patients are what?
leukopenia, anemia, and thrombocytopenia
_____ in SLE is common and usually reflects lymphopenia but can also be due to immunosuppressive therapies
Leukopenia (WBC < 4,000/mm3)
In SLE, ________ occurs in most patients during periods of disease activity but is also often due to hemodialysis
Anemia of chronic disease
______ anemia occurs in a small proportion of patients with SLE
Coombs-positive (antibodies to RBC’s) hemolytic
What does thrombocytopenia (platelet count < 100,000/mm3) result from in SLE?
increased phagocytosis of autoantibody-coated platelets by spleen, liver, bone marrow and lymph node macrophages and can occur in up to 25% of patients
When are patients with SLE prone to episodic thrombosis (increasing the risk for stroke, deep venous thrombosis, myocardial infarction, and spontaneous abortion)
When antiphospholipid antibodies (i.e., lupus anticoagulant [lupus antibody, lupus inhibitors] and/or anticardiolipin antibody) are present
What do Mucocutaneous Manifestations of SLE include?
-photosensitive rashes
- alopecia
- periungual telangiectasias
- Raynaud’s phenomenon
- skin ulceration secondary to vasculitis
The ______ rash (which affects fewer than half of SLE patients) and the _____ rash are the two most characteristic rashes of SLE
- malar or “butterfly”
- discoid
In SLE, Vasculitic skin lesions include what?
- subcutaneous nodules
- skin ulcers
- infarcts of skin or digits
What are the primary musculoskeletal disorders associated with SLE
Arthritis (with synovitis), arthralgia and myalgia
What is the most common initial manifestation of SLE.
Arthralgia with morning stiffness
More than 75% of SLE patients develop a _____ arthritis (specifically ________ with synovitis), which is symmetrical and non-erosive and which usually involves the hands, wrists, and knees
- true
- inflammatory polyarthritis
Diffuse and focal cerebral dysfunctions of SLE include what
- psychoses, delirium
- seizures
- cerebrovascular accidents (strokes)
- peripheral sensorimotor neuropathies
Oral lesions seen in patients with SLE include what
- mucosal inflammation and ulcerations
- lichenoid-appearing lesions
- angular cheilosis
- mucositis
- glossitis
Patients with SLE exhibit a high incidence of signs and symptoms of oral conditions, including what?
- glossodynia, dysgeusia, dysphagia, and xerostomia
- ~33% of patients with SLE also have Sjögren syndrome
SLE is most commonly diagnosed using what?
- the 2019 European League Against Rheumatism / American College of Rheumatology classification criteria for SLE.
(A diagnosis of SLE requires at least one “clinical criteria” and ≥ 10 points)
The most frequently positive (most sensitive) diagnostic laboratory test for SLE is the test for (generic) __________ in the serum, which is positive in 96% - 100% of patients with SLE
antinuclear antibody ANA (or antinuclear antibodies [ANAs])
T/F Clinicians should remember that the ANA test is specific to SLE, so they can rule out other diseases if positive.
FALSE
The clinician should remember that the ANA test is not specific for any one disease and is frequently positive in patients with autoimmune diseases other than SLE, including scleroderma, rheumatoid arthritis and Sjögren’s syndrome
Clinically, the most commonly used method to detect autoantibodies in SLE is what? What kind does it detect?
indirect immunofluorescence assay (indirect IFA), which detects a variety of nuclear autoantibodies, collectively referred to as antinuclear antibodies (ANA).
SLE is characterized by the production of numerous ANAs. What are they? (5)
- Anti-double-stranded DNA (anti-ds-DNA, anti-native DNA) (has the highest correlation and specificity for SLE)
- Rheumatoid factor (RF)
- Antibody to Smith (Sm) antigen (anti-Sm antibodies)
- Antibody to Ro (SS-A) antigen (anti-Ro antibodies)
- Antibody to La (SS-B) antigen (anti-La antibodies)
_______ staining of biopsy specimens has become an important aid in the diagnosis of the mucosal or skin lesions of SLE
Direct fluorescent antibody
More than 90% of patients with either DLE or SLE have deposits of ______ and _____ in the basement membrane zone
- immunoglobulin
- C3
Other important findings on routine laboratory test findings in patients with SLE include what?
- Anemia, thrombocytopenia, (which may occasionally be severe enough to cause purpura)
- Depressed complement levels (particularly C3 and C4), are also common
- Increased levels of globulins
- Biologic false-positive result on the serologic test for syphilis (STS) in ~ 15% patients (due to the presence of anticardiolipins).
What is rheumatoid arthritis (RA)?
A chronic systemic autoimmune inflammatory disease of unknown cause, chiefly affecting synovial membranes of multiple joints
Rheumatoid Arthritis has a wide clinical spectrum with considerable variability in _____ and _______ manifestations
- joint
- extra-articular
Is Rheumatoid arthritis (RA) more common in men or women?
RA is 3 to 5 times more common in women than in men
What is the usual age of onset of Rheumatoid arthritis (RA)
usual age at onset is 20 to 40 years, although RA may begin at any age
Approximately 50% of the risk of developing RA is related to ______ factors
genetic
Susceptibility to RA is linked to the ______ locus. There is also a strong association with a polymorphism in the PTPN22 gene, which encodes a ______ that is postulated to inhibit T cell activation
- HLA-DRB1
- tyrosine phosphatase
What is the onset of Rheumatoid arthritis (RA) like? What are the symptoms?
Usually gradual onset; common prodromal symptoms of weakness, fatigue, and anorexia.
What is the initial presentation of Rheumatoid arthritis (RA)
- multiple symmetric joint involvement, most often in the hands and feet
- Joint effusions, tenderness, and restricted motion are usually present early in the disease
What are eventual characteristics deformities of Rheumatoid arthritis (RA)
subluxations, dislocations, and joint contractures
Extra-articular findings in RA include what? (5)
- Tendon sheaths and bursae frequently affected by chronic inflammation
- Possible tendon rupture
- Rheumatoid nodules over bony prominences such as the elbow and shaft of the ulna
- Splenomegaly, pericarditis, and vasculitis
- Findings of carpal tunnel syndrome resulting from flexor tenosynovitis
What do the pathologic findings in the joint include for rheumatoid arthritis (RA)
chronic synovitis with pannus formation. The pannus erodes cartilage, bone, ligaments, and tendons
In the acute phase of RA pathology, ______ and other manifestations of inflammation are common
effusion
In the late stage of RA pathology, organization may result in fibrous ______; true bony ______ is rare
ankylosis
(for both blanks)
In both acute and chronic phases of rheumatoid arthritis (RA), ______ of soft tissues around the joints may be prominent and is a significant factor in ______ damage.
- inflammation
- joint
What microscopic findings are most characteristic of RA?
those of the subcutaneous (rheumatoid) nodule
What is a subcutaneous (rheumatoid) nodule in RA?
This is a granuloma with a central zone of fibrinoid necrosis surrounding a palisade of radially arranged elongated connective tissue cells, and a margin of chronic granulation tissue
RA has features of a ______ hypersensitivity reaction directed against articular cartilage, bone, and other joint tissues
type IV
The synovium of RA-affected joints contains what?
germinal centers with secondary follicles and abundant plasma cells that produce autoantibodies
What are examples of autoantibodies produced by plasma cells in RA?
- rheumatoid factor (RF) [autoantibody against the Fc portion of IgG]
- anti-cyclic citrullinated peptide antibodies (anti-CCP) [or anti-citrullinated protein antibodies (ACPA)]
What do cytokines produced by the activated T cells do in rheumatoid arthritis (RA)
- recruit macrophages, whose products cause tissue injury
- activate resident synovial cells to produce proteolytic enzymes, such as collagenase, that facilitate destruction of the cartilage, ligaments, and tendons of the joints
What contributes to the bone destruction in RA
Increased osteoclast activity in the joints
What increases osteoclast activity in rheumatoid arthritis (RA)
This may be caused by the production of the TNF family cytokines by activated T cells
_______ is a nonspecific assay for pentameric IgM antibodies in the blood and will be present in 70 to 80% of patients with RA.
Rheumatoid factor (RF)
20% of RA patients will remain Rheumatoid factor (RF)______ despite other signs RA
negative
_______ are more specific than Rheumatoid factor (RF) for RA (up to 95% - 98% specificity)
Anti-citrullinated protein antibodies (ACPA)
______ is positive in 30% - 60% of patients with RA
Anti-nuclear antibody (ANA)
Elevated acute phase reactants are common in RA due to inflammation. What are the examples?
- Erythrocyte sedimentation rate (ESR)
- Elevated C-reactive protein (CRP)
In rheumatoid arthritis (RA), lab findings show mild, normocytic normochromic _____ in ~ 80% of patients and ______ joint fluid
- anemia
- turbid
What are possible complications of rheumatoid arthritis (RA)
- Erosive arthritis and joint destruction
- Dental:
- 25 - 35% of RA patients have (secondary) Sjögren’s syndrome
- The TMJ is involved in 75% of patients with RA
What is Sjögren syndrome (SS)
a chronic disease characterized by dry eyes (keratoconjunctivitis sicca) and dry mouth (xerostomia) resulting from immunologically mediated destruction of the lacrimal and salivary glands.
Approximately 90% of SS cases occur in ____ between the ages of _____ years
- women (female-tomale ratio is 9:1)
- 35 and 45
What are the primary and secondary forms of Sjögren syndrome (SS)
- Primary = occurs as an isolated disorder, also known as the sicca syndrome
- secondary = more often (~60%), in association with another autoimmune disease
What disorders are often associated with Sjögren syndrome (SS)
- rheumatoid arthritis is the most common
- some patients have SLE, polymyositis, scleroderma, vasculitis, mixed connective tissue disease, or thyroiditis
Secondary SS is seen in 25 - 35% of patients with _____, and ~ 33% of patients with ______
- rheumatoid arthritis
- SLE
Although the pathogenesis of Sjögren’s syndrome is not fully understood, what is thought to be the initiating factor?
may be a viral infection (e.g., EBV, Coxsackie virus) of the salivary glands, which causes local cell death and release of tissue self-antigens
In the pathogenesis of Sjögren’s syndrome, in genetically susceptible individuals, _____ cells and _____ cells specific for self-antigens may have escaped tolerance and are able to react
- CD4+ T
- B
In the pathogenesis of Sjögren’s syndrome, what is the result when CD4+ T cells and B cells specific for self-antigens escape tolerance and react?
The result is inflammation, tissue damage, and, eventually, fibrosis
What are the major targets of Sjögren Syndrome
Lacrimal and salivary glands
Both forms of SS (primary or secondary) can have _______ manifestations that can potentially effect all major organ systems, as well as an increased risk for the development of ________
- extraglandular
- lymphoma
Most individuals with SS present with what symptoms?
“sicca” symptoms, such as xerophthalmia (dry eyes), xerostomia (dry mouth)
SS classically manifests with what?
painless, intermittent enlargement of the parotid, generally beginning unilaterally
What can enlargement of the parotid progress to in Sjögren Syndrome
chronic salivary gland (typically bilateral) enlargement
Patients with Sjögren Syndrome may describe dry mouth how? (4)
- Inability to eat dry food (e.g., crackers) because it sticks to the roof the mouth
- Tongue sticking to the roof of the mouth
- Difficulty speaking for long periods of time or the development of hoarseness
- Difficulty wearing dentures
In Sjögren Syndrome dry eyes may be described as red, itchy, and painful. However, the most typical complaint is what?
gritty or sandy sensation in the eyes.
About 25% of patients with SS have some degree of ______ manifestations of the disease
extraglandular
Skin manifestations of Sjögren Syndrome may include what?
- palpable or nonpalpable purpura, papules, urticarial lesions, and annular lesions
- Xerosis is frequently found on examination.
Neurologic components of Sjögren Syndrome may include what?
peripheral and cranial neuropathies and a multiple sclerosis “look-alike” CNS disease
Lung involvement in SS may include what?
- tracheobronchitis
- bronchiectasis, interstitial pneumonitis, and fibrosis
Renal involvment of Sjögren Syndrome may include what?
interstitial nephritis, renal tubular acidosis, and hyposthenuria (urine with an osmolality less than that of plasma) with glomerulonephritis
What is the Schirmer test used for?
It can be used to measure the production of tears and helps establish the presence of xerophthalmia in SS
In Sjögren Syndrome diagnosis, ______ is a good measure of the degree of decreased salivary flow and helps establish the presence of xerostomia
Sialometry
The ______ biopsy specimen finding is considered by some to be the best sole diagnostic criterion for the salivary component of Sjögren Syndrome
minor salivary gland
What is the earliest histologic finding in both the major and minor salivary glands from salivary gland biopsy?
periductal and perivascular lymphocytic infiltration
In Sjögren Syndrome, about 75% of patients are positive for ______ regardless of whether coexisting ______ is present or not
- rheumatoid factor (RF)
- rheumatoid arthritis
In Primary Sjögren Syndrome, ______ (most commonly in a fine, speckled pattern) are detected in up to 83% of patients
ANA’s
What are the two autoantibodies directed against two ribonucleoprotein antigens in patients with SS?
- SS-A (Ro): slightly more common
- SS-B (La)
What do the autoantibodies SS-A (Ro) and SS-B (La) represent when identified in Sjögren Syndrome?
represent the best serologic autoantibody markers associated with SS
Sjögren’s Syndrome gives patients increased risk and susceptibility to what?
salivary gland infections (parotitis) and/or gland obstructions that present as acute exacerbations of chronically enlarged glands
Changes secondary to xerostomia in Sjögren’s Syndrome include? (4)
- Oral mucosal atrophy, with inflammatory fissuring and ulceration
- Increased incidence of caries and periodontal disease
- Dysphagia and dysgeusia
- Development of oral candidiasis occurs in up to 80% of patients
One complication of SS is that the lack of tears leads to _______
keratoconjunctivitis sicca
A severe complication of Sjögren’s Syndrome is that _______ (mostly of the B-cell type) have developed in the salivary glands and lymph nodes in some patients
Non-Hodgkin lymphomas
it is believed that patients with Sjögren’s syndrome have up to a 40-fold increased risk of developing _______
lymphoid malignancies
What is Amyloidosis
a diverse family of rare, chronic infiltrative localized or multisystem disorders characterized by the presence of extracellular deposits of insoluble fibrillar proteins
What is each variety of amyloidosis identified by?
immunochemical nature of the amyloid protein fibrils
What is the most common syndrome in amyloidosis?
nephrotic syndrome / renal failure
(Amyloidosis is an important cause of nephrotic syndrome, renal insufficiency, and progressive renal failure)
What is the structure of amyloid?
- not a single substance but a group of substances that share a common physical structure
- Always has a beta-pleated sheet configuration
What does amyloidosis result from?
abnormal folding of proteins, which are deposited as fibrils in extracellular tissues and disrupt normal function
In patients with amyloidosis, a soluble circulating protein (________) found in the serum is deposited in tissues as insoluble ______ sheets
- serum amyloid P [SAP]
- β-pleated
Amyloid deposits cause tissue injury and impair normal function by causing _____ on cells and tissues
pressure
T/F Amyloid deposits in tissues evoke an inflammatory response
Amyloid deposits in tissues do not evoke an inflammatory response
What three forms of amyloid proteins are the most common?
- AL (amyloid light chain)
- AA (amyloid-associated)
- Aβ amyloid
What is AL (amyloid light chain) derived from?
plasma cells and contains immunoglobulin light chains
What is the AA (amyloid-associated) form of protein derived from?
derived from serum amyloid-associated protein (SAA) synthesized by liver cells under the influence of cytokines such as IL-6 and IL-1 that are produced during inflammation
What is the Aβ amyloid form of protein derived from? Where is it found?
- found in the cerebral lesions of patients with Alzheimer’s disease
- derived from a transmembrane glycoprotein called amyloid precursor protein (APP)
Amyloid is characteristically stained by _____ dye, demonstrating apple green ______ when viewed under _____light and confirming the suspected presence of amyloid.
- Congo red
- birefringence
- polarized
What is Primary amyloidosis (immunocytic dyscrasia amyloidosis) caused by?
deposition of amyloid fibrils derived from immunoglobulin light chains, referred to as AL (amyloid light chain) protein
Primary amyloidosis (immunocytic dyscrasia amyloidosis) includes the amyloidosis frequently associated with _____ disorders such as _______ and Waldenström macroglobulinemia
- plasma cell
- multiple myeloma
What is primary amyloidosis most characteristically marked by?
amyloid deposition in tissues of mesodermal origin, such as heart, muscle, and tongue
Primary amyloidosis may involve the ____, with amyloid deposits in the glomerular mesangium as well as in the interstitial tissue between _______
- kidney
- tubules
What is Secondary amyloidosis (reactive systemic amyloidosis) marked by?
deposition of fibrils consisting of the amyloid protein called AA protein, which is formed from a precursor, serum amyloid-associated protein (SAA)
In secondary amyloidosis, what leads to increased serum amyloid-associated protein (SAA)
chronic inflammatory disease such as rheumatoid arthritis, tuberculosis, osteomyelitis, syphilis, or leprosy
What are examples of noninflammatory disorders that secondary amyloidosis can complicate?
renal cell carcinoma and Hodgkin’s disease
Secondary amyloidosis (reactive systemic amyloidosis) usually involves parenchymatous organs, especially which ones?
kidney (nephrotic syndrome is very common), liver, adrenals, pancreas, lymph nodes, and spleen
