**Question:** In which of the following c-ANCA is seen?

A. Proteinase 3 (PR3)
B. Myeloperoxidase (MPO)
C. Neither
D. Both

**Core Concept:**
Antineutrophil cytoplasmic antibodies (ANCA) are a type of autoantibodies that target specific enzymes present in neutrophil granules. There are two main types of ANCA:

1. c-ANCA (cytoplasmic ANCA): ANCA that bind to intracellular antigens within neutrophil granules.
2. p-ANCA (perinuclear ANCA): ANCA that bind to antigens on the surface of neutrophil nuclei or cytoplasmic extensions called pseudopodia.

**Why the Correct Answer is Right:**
The correct answer is "D. Both" because c-ANCA can be seen in two conditions:

1. Proteinase 3 (PR3) ANCA: PR3 is an enzyme found in neutrophil granules and is commonly associated with Wegener's granulomatosis, a systemic necrotizing vasculitis.
2. Myeloperoxidase (MPO) ANCA: MPO is another enzyme found in neutrophil granules and is associated with microscopic polyangiitis (formerly known as Churg-Strauss syndrome), a systemic necrotizing vasculitis.

**Why Each Wrong Option is Incorrect:**

A. **Neither:** Selecting this option would mean that neither c-ANCA is present, which is incorrect as both PR3 and MPO are commonly associated with specific vasculitides.
B. **MPO only:** This option inaccurately assumes that MPO is the sole ANCA associated with vasculitis, which is not true. Both PR3 and MPO are involved in the pathogenesis of respective vasculitides.
C. **PR3 only:** Similar to option B, this option disregards the presence of MPO in neutrophils and the association with microscopic polyangiitis.

**Clinical Pearl:**
ANCA testing plays a crucial role in diagnosing vasculitis, particularly Wegener's granulomatosis and microscopic polyangiitis. A positive ANCA test, particularly c-ANCA, indicates the presence of a vasculitis, and further evaluation with imaging studies and biopsy can confirm the diagnosis.